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A comprehensive in silico genome-wide identification and characterization of SQUAMOSA promoter binding protein (SBP) gene family in Musa acuminata
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2025-01-23 DOI: 10.1016/j.jgeb.2025.100461
Israt Jahan Mouri , Md. Shariful Islam
One of the largest and most significant transcription factor gene families in plants is the SQUAMOSA promoter binding protein (SBP) gene family and they perform critical regulatory roles in floral enhancement, fruit development, and stress resistance. The SBP protein family (also known as SPL) has not yet been thoroughly studied in the staple fruit crop, banana. A perennial monocot plant, banana is essential for ensuring food and nutrition security. This work detected 41 SBP genes in the banana species Musa acuminata. The MaSBPs were subsequently elucidated by investigating their gene structure, chromosomal position, RNA-Seq data, along with evolutionary connections with Arabidopsis and rice. Sequence alignment of MaSBPs revealed that all genes included a domain of two Zn finger motifs (CCCH and CCHC motifs) with an overlapping nuclear localization signal region. The conserved motifs sequence in the inferred MaSBP proteins were quite comparable. According to findings, the time frame of divergence for duplicated MaSBP gene pairs ranged from 42.39 to 109.11 million years and the dicot Arabidopsis and monocotyledonous plant banana diverged before the division of banana and monocot rice. Moreover, cis-acting element and GO annotation analysis exhibited possible biological activities of MaSBPs in flower development, phytohormone regulation, and stress tolerance. RNA-Seq expression profiling exhibited that genes MaSBP-3, MaSBP-20, MaSBP-37, MaSBP-40 were more expressed during floral and fruit development stage. The foundation for additional investigation of SBP protein sequences in other plants can be laid out by this study, which will shed light on some of their crucial biological functions.
{"title":"A comprehensive in silico genome-wide identification and characterization of SQUAMOSA promoter binding protein (SBP) gene family in Musa acuminata","authors":"Israt Jahan Mouri ,&nbsp;Md. Shariful Islam","doi":"10.1016/j.jgeb.2025.100461","DOIUrl":"10.1016/j.jgeb.2025.100461","url":null,"abstract":"<div><div>One of the largest and most significant transcription factor gene families in plants is the SQUAMOSA promoter binding protein (<em>SBP</em>) gene family and they perform critical regulatory roles in floral enhancement, fruit development, and stress resistance. The <em>SBP</em> protein family (also known as <em>SPL</em>) has not yet been thoroughly studied in the staple fruit crop, banana. A perennial monocot plant, banana is essential for ensuring food and nutrition security. This work detected 41 <em>SBP</em> genes in the banana species <em>Musa acuminata</em>. The <em>MaSBPs</em> were subsequently elucidated by investigating their gene structure, chromosomal position, RNA-Seq data, along with evolutionary connections with Arabidopsis and rice. Sequence alignment of <em>MaSBPs</em> revealed that all genes included a domain of two Zn finger motifs (CCCH and CCHC motifs) with an overlapping nuclear localization signal region. The conserved motifs sequence in the inferred <em>MaSBP</em> proteins were quite comparable. According to findings, the time frame of divergence for duplicated <em>MaSBP</em> gene pairs ranged from 42.39 to 109.11 million years and the dicot Arabidopsis and monocotyledonous plant banana diverged before the division of banana and monocot rice. Moreover, <em>cis</em>-acting element and GO annotation analysis exhibited possible biological activities of <em>MaSBPs</em> in flower development, phytohormone regulation, and stress tolerance. RNA-Seq expression profiling exhibited that genes <em>MaSBP</em>-3, <em>MaSBP</em>-20, <em>MaSBP</em>-37, <em>MaSBP</em>-40 were more expressed during floral and fruit development stage. The foundation for additional investigation of <em>SBP</em> protein sequences in other plants can be laid out by this study, which will shed light on some of their crucial biological functions.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100461"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A comparative study on antioxidant properties, total phenolics, total flavonoid contents, and cytotoxic properties of marine green microalgae and diatoms
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2025-01-22 DOI: 10.1016/j.jgeb.2024.100456
Umme Tamanna Ferdous , Armania Nurdin , Saila Ismail , Khozirah Shaari , Zetty Norhana Balia Yusof
Despite having valuable and novel metabolites, the marine microalgae species are still not thoroughly investigated for their pharmaceutical and nutraceutical importance. Therefore, this study was focused on investigating the crude extracts of marine green microalgae species, Tetraselmis sp., Nannochloropsis sp., and diatoms Chaetoceros sp., and Thalassiosira sp., isolated from the Malaysian coastal region in terms of their antioxidant activity, total phenolics, total flavonoid contents and cytotoxicity against human breast cancer cells, MCF-7. Among twenty-eight crude extracts, Tetraselmis ethanol and ethyl acetate extract showed the highest amount of total phenolic (19.87 mg GAE/g), and total flavonoid content (38.58 mg QE/g of extract), respectively. From the antioxidant assays, methanol and ethyl acetate extract of Tetraselmis sp. exhibited significantly higher (p < 0.05) antioxidant activities, revealed through DPPH (54.41 ± 1.18 mg Trolox Equivalent Antioxidant Capacity or TEAC/g extract) and ABTS (41.57 ± 0.83 mg TEAC/g extract) radical scavenging activities, respectively than the rest. Ethyl acetate extract of Tetraselmis sp. also showed high ferric reducing power (113.46 ± 4.83 mg TEAC/g extract). On the contrary, methanol and ethyl acetate extract of Chaetoceros sp. showed the highest cytotoxicity towards MCF-7 and reduced the cell viability to 21.26 % and 21.56 %, respectively. The data suggest that marine diatom Chaetoceros sp. has a good cytotoxic effect on MCF-7, while marine green microalga Tetraselmis sp. has good radical scavenging and ferric reduction capabilities, warranting further investigation along with their metabolic profiling, cancer cell killing mechanism and extensive in vivo study.
{"title":"A comparative study on antioxidant properties, total phenolics, total flavonoid contents, and cytotoxic properties of marine green microalgae and diatoms","authors":"Umme Tamanna Ferdous ,&nbsp;Armania Nurdin ,&nbsp;Saila Ismail ,&nbsp;Khozirah Shaari ,&nbsp;Zetty Norhana Balia Yusof","doi":"10.1016/j.jgeb.2024.100456","DOIUrl":"10.1016/j.jgeb.2024.100456","url":null,"abstract":"<div><div>Despite having valuable and novel metabolites, the marine microalgae species are still not thoroughly investigated for their pharmaceutical and nutraceutical importance. Therefore, this study was focused on investigating the crude extracts of marine green microalgae species, <em>Tetraselmis</em> sp., <em>Nannochloropsis</em> sp., and diatoms <em>Chaetoceros</em> sp., and <em>Thalassiosira</em> sp., isolated from the Malaysian coastal region in terms of their antioxidant activity, total phenolics, total flavonoid contents and cytotoxicity against human breast cancer cells, MCF-7. Among twenty-eight crude extracts, <em>Tetraselmis</em> ethanol and ethyl acetate extract showed the highest amount of total phenolic (19.87 mg GAE/g), and total flavonoid content (38.58 mg QE/g of extract), respectively. From the antioxidant assays, methanol and ethyl acetate extract of <em>Tetraselmis</em> sp. exhibited significantly higher (p &lt; 0.05) antioxidant activities, revealed through DPPH (54.41 ± 1.18 mg Trolox Equivalent Antioxidant Capacity or TEAC/g extract) and ABTS (41.57 ± 0.83 mg TEAC/g extract) radical scavenging activities, respectively than the rest. Ethyl acetate extract of <em>Tetraselmis</em> sp. also showed high ferric reducing power (113.46 ± 4.83 mg TEAC/g extract). On the contrary, methanol and ethyl acetate extract of <em>Chaetoceros</em> sp. showed the highest cytotoxicity towards MCF-7 and reduced the cell viability to 21.26 % and 21.56 %, respectively. The data suggest that marine diatom <em>Chaetoceros</em> sp. has a good cytotoxic effect on MCF-7, while marine green microalga <em>Tetraselmis</em> sp. has good radical scavenging and ferric reduction capabilities, warranting further investigation along with their metabolic profiling, cancer cell killing mechanism and extensive <em>in vivo</em> study.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100456"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Screening and genomic evaluation of keratinolytic protease producing Chryseobacterium sp. from tannery waste and its potential application in dehairing of goat skin
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2025-01-19 DOI: 10.1016/j.jgeb.2025.100458
Taslima Akter , Murshed Hasan Sarkar , Shashanka Shekhar Sarker , Nourin Tarannum , Showti Raheel Naser , Sanjana Fatema Chowdhury , Sahana Parveen
Lime and Na2S, used in dehairing in the tannery industry, cause the generation of toxic wastes. Ecological security and financial issues demand a look for innovative approaches to leather dehairing free from pollution. The primary goal of this investigation was to explore keratinolytic protease producing bacteria from tannery waste, their genomic evaluation and to assess their possible use in the dehairing process. A newly isolated Gram-negative bacterium (LRI-TA6) was characterized and checked for its keratinolytic protease producing ability. The strain was identified as Chryseobacterium cucumeris through whole genome sequencing. The genome was 4,541,898 bp in size and contain 4,426 protein coding sequences (CDS) with 36.38 % of GC content. Twenty-five open reading frames (CDS) were found as protease producing genes notably DegQ (serine protease), DegS, and ATP-dependent protease DP (EC 3.4.21.-). The isolate revealed enzyme production throughout an extended pH range of 5.0 to 8.0, and a broad temperature range of 10 °C to 38 °C. The isolate LRI-TA6 was sensitive to all five antibiotics (amoxicillin, tetracycline, gentamicin, ciprofloxacin, and vancomycin) with zone diameter ranges from 17.2 ± 0.8 to 32 ± 0.0 mm. The enzyme was shown to have 29.9 ± 6.7 and 83.6 ± 0.2 U/ml of keratinolytic and proteolytic activity, respectively. By employing crude keratinase, the removal of hair from goat skin was accomplished in 18 h. This study is the first report to isolate and characterize C. cucumeris from tannery waste and also the amazing 18 h dehairing capabilities and thus might be utilized for further studies towards commercial synthesis of keratinase for use in leather processing sectors.
{"title":"Screening and genomic evaluation of keratinolytic protease producing Chryseobacterium sp. from tannery waste and its potential application in dehairing of goat skin","authors":"Taslima Akter ,&nbsp;Murshed Hasan Sarkar ,&nbsp;Shashanka Shekhar Sarker ,&nbsp;Nourin Tarannum ,&nbsp;Showti Raheel Naser ,&nbsp;Sanjana Fatema Chowdhury ,&nbsp;Sahana Parveen","doi":"10.1016/j.jgeb.2025.100458","DOIUrl":"10.1016/j.jgeb.2025.100458","url":null,"abstract":"<div><div>Lime and Na<sub>2</sub>S, used in dehairing in the tannery industry, cause the generation of toxic wastes. Ecological security and financial issues demand a look for innovative approaches to leather dehairing free from pollution. The primary goal of this investigation was to explore keratinolytic protease producing bacteria from tannery waste, their genomic evaluation and to assess their possible use in the dehairing process. A newly isolated Gram-negative bacterium (LRI-TA6) was characterized and checked for its keratinolytic protease producing ability. The strain was identified as <em>Chryseobacterium cucumeris</em> through whole genome sequencing. The genome was 4,541,898 bp in size and contain 4,426 protein coding sequences (CDS) with 36.38 % of GC content. Twenty-five open reading frames (CDS) were found as protease producing genes notably DegQ (serine protease), DegS, and ATP-dependent protease DP (EC 3.4.21.-). The isolate revealed enzyme production throughout an extended pH range of 5.0 to 8.0, and a broad temperature range of 10 °C to 38 °C. The isolate LRI-TA6 was sensitive to all five antibiotics (amoxicillin, tetracycline, gentamicin, ciprofloxacin, and vancomycin) with zone diameter ranges from 17.2 ± 0.8 to 32 ± 0.0 mm. The enzyme was shown to have 29.9 ± 6.7 and 83.6 ± 0.2 U/ml of keratinolytic and proteolytic activity, respectively. By employing crude keratinase, the removal of hair from goat skin was accomplished in 18 h. This study is the first report to isolate and characterize <em>C. cucumeris</em> from tannery waste and also the amazing 18 h dehairing capabilities and thus might be utilized for further studies towards commercial synthesis of keratinase for use in leather processing sectors.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100458"},"PeriodicalIF":3.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Process optimization and extraction of alkaline protease from halotolerant Streptomyces sp. VITGS3 and its use as a contact lens cleaner
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2025-01-18 DOI: 10.1016/j.jgeb.2025.100459
Gargi Sarkar, K. Prem Anand, M.A. Jayasri, K. Suthindhiran
Marine halotolerant actinobacteria are robust microbes poorly explored and barely cultivable in nature. They are a trove of various secondary metabolites and enzymes, especially the alkaline proteases withstanding higher temperatures, pH, and salinity, making them an ideal source with versatile commercial and therapeutic values. This study focuses on extracting and optimizing alkaline protease production from Streptomyces sp. VITGS3 isolated from Puthuvypeen, Kerala. The protease production was optimized by Response Surface Methodology (RSM) using the Box-Behnken model, which used rice bran, wheat bran, skim milk, and casein as substrates. The maximum protease was produced (357 U/mL) using wheat bran (5.5 % w/v) as substrate at pH 9 and incubated at 45 °C for 9 days. The Michaelis-Menten model’s enzyme kinetics exhibited a Km value of 1.42 µM, a Vmax of 201.64 µM·min−1, V0 of 5.59 µM·min−1, and Kcat 70013.89 min−1 suggesting a higher affinity of the enzyme for the substrate (1 % w/v casein). In addition, the protease was inhibited by the phenylmethylsulphonyl fluoride (PMSF), suggesting it belongs to the serine protease family. Finally, the application studies as contact lens cleaners showcased that the isolated protease effectively degraded the protein deposits present in the artificial tear solution without affecting the light transmittance. This is a milestone in the implication of protease on therapeutic applications and further studies on protein specificity, sustained releases, and combination strategies, resulting in crucial challenges in long-term studies, cross-reactivity, storage, and cost-effectiveness.
{"title":"Process optimization and extraction of alkaline protease from halotolerant Streptomyces sp. VITGS3 and its use as a contact lens cleaner","authors":"Gargi Sarkar,&nbsp;K. Prem Anand,&nbsp;M.A. Jayasri,&nbsp;K. Suthindhiran","doi":"10.1016/j.jgeb.2025.100459","DOIUrl":"10.1016/j.jgeb.2025.100459","url":null,"abstract":"<div><div>Marine halotolerant actinobacteria are robust microbes poorly explored and barely cultivable in nature. They are a trove of various secondary metabolites and enzymes, especially the alkaline proteases withstanding higher temperatures, pH, and salinity, making them an ideal source with versatile commercial and therapeutic values. This study focuses on extracting and optimizing alkaline protease production from <em>Streptomyces</em> sp. VITGS3 isolated from Puthuvypeen, Kerala. The protease production was optimized by Response Surface Methodology (RSM) using the Box-Behnken model, which used rice bran, wheat bran, skim milk, and casein as substrates. The maximum protease was produced (357 U/mL) using wheat bran (5.5 % w/v) as substrate at pH 9 and incubated at 45 °C for 9 days. The Michaelis-Menten model’s enzyme kinetics exhibited a K<sub>m</sub> value of 1.42 µM, a V<sub>max</sub> of 201.64 µM·min<sup>−1</sup>, V<sub>0</sub> of 5.59 µM·min<sup>−1</sup>, and K<sub>cat</sub> 70013.89 min<sup>−1</sup> suggesting a higher affinity of the enzyme for the substrate (1 % w/v casein). In addition, the protease was inhibited by the phenylmethylsulphonyl fluoride (PMSF), suggesting it belongs to the serine protease family. Finally, the application studies as contact lens cleaners showcased that the isolated protease effectively degraded the protein deposits present in the artificial tear solution without affecting the light transmittance. This is a milestone in the implication of protease on therapeutic applications and further studies on protein specificity, sustained releases, and combination strategies, resulting in crucial challenges in long-term studies, cross-reactivity, storage, and cost-effectiveness.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100459"},"PeriodicalIF":3.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2025-01-16 DOI: 10.1016/j.jgeb.2025.100457
Saurav Kumar Mishra , Neeraj Kumar , Zsolt Tóth , Yousef A. Bin Jardan , Shopnil Akash , John J. Georrge

Background

Acquired Immunodeficiency Syndrome (AIDS) is a critical global health issue caused by the human immunodeficiency virus (HIV). It has different strains and subtypes; among these, Subtype C accounts for higher infection rates than others. Despite its high prevalence, the molecular interactions with host receptors, specifically CD4, have not yet been explored.

Methods

This study investigates the molecular interactions between HIV subtype C and the CD4 receptor via docking and dynamics approach. Four HIV targets were examined, and their structure was modelled. Subsequently, these models were docked with the CD4 to analyze their binding interaction. The stability was examined over 200 simulations via Desmond software, and trajectories were analyzed, followed by Root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the radius of gyration (Rg), PCA (principal component analysis), etc., to assess their stability and interaction dynamics.

Results

The four target structures were modelled, and their quality was validated. Further, the docking analysis with CD4 revealed that the Envelope glycoprotein has −13.6 kcal/mol, protease has −11.2 kcal/mol, Reverse transcriptase has −12.4 kcal/mol, and integrase has −13.1 kcal/mol binding affinity towards it, followed by the number of hydrogen bond, such as 9, 6, 11, 6. The simulation over 200 ns demonstrated that the average RMSD for each complex started stabilizing within the 0.9 Å − 3.4 Å, followed by 25–50 ns, whereas the RMSF, Rg and PCA revealed the relative compactness and flexibility varied across different viral targets.

Conclusions

The study successfully identified the interactive residues of HIV subtype C toward the CD4 receptor. The binding affinities and stability data provide valuable insights into Subtype C’s molecular interactions with the host, and these findings underscore the potential for developing treatments that disrupt these interactions to combat HIV more effectively.
{"title":"Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach","authors":"Saurav Kumar Mishra ,&nbsp;Neeraj Kumar ,&nbsp;Zsolt Tóth ,&nbsp;Yousef A. Bin Jardan ,&nbsp;Shopnil Akash ,&nbsp;John J. Georrge","doi":"10.1016/j.jgeb.2025.100457","DOIUrl":"10.1016/j.jgeb.2025.100457","url":null,"abstract":"<div><h3>Background</h3><div>Acquired Immunodeficiency Syndrome (AIDS) is a critical global health issue caused by the human immunodeficiency virus (HIV). It has different strains and subtypes; among these, Subtype C accounts for higher infection rates than others. Despite its high prevalence, the molecular interactions with host receptors, specifically CD4, have not yet been explored.</div></div><div><h3>Methods</h3><div>This study investigates the molecular interactions between HIV subtype C and the CD4 receptor via docking and dynamics approach. Four HIV targets were examined, and their structure was modelled. Subsequently, these models were docked with the CD4 to analyze their binding interaction. The stability was examined over 200 simulations via Desmond software, and trajectories were analyzed, followed by Root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the radius of gyration (Rg), PCA (principal component analysis), etc., to assess their stability and interaction dynamics.</div></div><div><h3>Results</h3><div>The four target structures were modelled, and their quality was validated. Further, the docking analysis with CD4 revealed that the Envelope glycoprotein has −13.6 kcal/mol, protease has −11.2 kcal/mol, Reverse transcriptase has −12.4 kcal/mol, and integrase has −13.1 kcal/mol binding affinity towards it, followed by the number of hydrogen bond, such as 9, 6, 11, 6. The simulation over 200 ns demonstrated that the average RMSD for each complex started stabilizing within the 0.9 Å − 3.4 Å, followed by 25–50 ns, whereas the RMSF, Rg and PCA revealed the relative compactness and flexibility varied across different viral targets.</div></div><div><h3>Conclusions</h3><div>The study successfully identified the interactive residues of HIV subtype C toward the CD4 receptor. The binding affinities and stability data provide valuable insights into Subtype C’s molecular interactions with the host, and these findings underscore the potential for developing treatments that disrupt these interactions to combat HIV more effectively.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100457"},"PeriodicalIF":3.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Telomeric RNA quadruplexes as targets for cancer prevention: The therapeutic potential of agonodepsides
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-31 DOI: 10.1016/j.jgeb.2024.100454
Gourav Choudhir , Sushil Kumar , Mohammad Shahid , Anas Shamsi , Asimul Islam

Background

Cancer remains an awful challenge, despite years of targeting proteins to control its relentless growth and spread. Fungal metabolites, a treasure of natural chemicals, offer a glimmer of hope. Telomeres, the cellular “caps,” are a focal point in cancer research. This study explores the potential of stabilizing Telomeric Repeats-containing RNA G-quadruplex (TERRA G4) structures within telomeres. This stabilization could block telomerase, the enzyme that repairs telomeres, and potentially trigger cancer cell death. Agonodepsides A and B, two promising fungal metabolites, were chosen to investigate this exciting possibility.

Methods

Agonodepside A and B were initially screened for drug likeness employing SwissAdme. AutoDock Vina was used for molecular docking, and ligands and TERRA G4 were prepared using PyRx and MGL tool. Discovery Studio software was utilized for the visualization of interactions between ligands and TERRA G4. For validation of docking results MD simulation for control and complexes was carried out for 250 ns and trajectories were analyzed for different parameters. MMPBSA was used to calculate binding free energy for control and complexes. To find the stable and lower energy states of complexes in comparison to control principal component analysis (PCA) and free energy landscape (FEL) were conducted.

Results

Absorption, distribution, metabolism, and excretion (ADME) of both agonodepsides followed Lipinski’s rule of five with zero violation. Molecular docking revealed several key interactions including hydrogen bonds, van der Waals interactions, π-alkyl and π-anion. MD simulation revealed that Agonodepside A interact with TERRA G4 and stabilize it while Agonodepside B interactions were transient. The MMPBSA binding free energy calculation, PCA and free energy landscapes supported the docking and MD simulation results.

Conclusion

Lichenized fungi produce agonodepsides A and B, may fight cancer by targeting telomeres. Agonodepside A binds more strongly to telomeres than B, potentially blocking enzyme telomerase. Further studies are required to validate these findings and evaluate potential safety concerns.
{"title":"Telomeric RNA quadruplexes as targets for cancer prevention: The therapeutic potential of agonodepsides","authors":"Gourav Choudhir ,&nbsp;Sushil Kumar ,&nbsp;Mohammad Shahid ,&nbsp;Anas Shamsi ,&nbsp;Asimul Islam","doi":"10.1016/j.jgeb.2024.100454","DOIUrl":"10.1016/j.jgeb.2024.100454","url":null,"abstract":"<div><h3>Background</h3><div>Cancer remains an awful challenge, despite years of targeting proteins to control its relentless growth and spread. Fungal metabolites, a treasure of natural chemicals, offer a glimmer of hope. Telomeres, the cellular “caps,” are a focal point in cancer research. This study explores the potential of stabilizing Telomeric Repeats-containing RNA G-quadruplex (TERRA G4) structures within telomeres. This stabilization could block telomerase, the enzyme that repairs telomeres, and potentially trigger cancer cell death. Agonodepsides A and B, two promising fungal metabolites, were chosen to investigate this exciting possibility.</div></div><div><h3>Methods</h3><div>Agonodepside A and B were initially screened for drug likeness employing SwissAdme. AutoDock Vina was used for molecular docking, and ligands and TERRA G4 were prepared using PyRx and MGL tool. Discovery Studio software was utilized for the visualization of interactions between ligands and TERRA G4. For validation of docking results MD simulation for control and complexes was carried out for 250 ns and trajectories were analyzed for different parameters. MMPBSA was used to calculate binding free energy for control and complexes. To find the stable and lower energy states of complexes in comparison to control principal component analysis (PCA) and free energy landscape (FEL) were conducted.</div></div><div><h3>Results</h3><div>Absorption, distribution, metabolism, and excretion (ADME) of both agonodepsides followed Lipinski’s rule of five with zero violation. Molecular docking revealed several key interactions including hydrogen bonds, van der Waals interactions, π-alkyl and π-anion. MD simulation revealed that Agonodepside A interact with TERRA G4 and stabilize it while Agonodepside B interactions were transient. The MMPBSA binding free energy calculation, PCA and free energy landscapes supported the docking and MD simulation results.</div></div><div><h3>Conclusion</h3><div>Lichenized fungi produce agonodepsides A and B, may fight cancer by targeting telomeres. Agonodepside A binds more strongly to telomeres than B, potentially blocking enzyme telomerase. Further studies are required to validate these findings and evaluate potential safety concerns.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100454"},"PeriodicalIF":3.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-throughput screening of natural antiviral drug candidates against white spot syndrome virus targeting VP28 in Penaeus monodon: Computational drug design approaches
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-28 DOI: 10.1016/j.jgeb.2024.100455
Md. Touki Tahamid Tusar , Zubaer Hossen , Hafizur Rahman Gazi , Niamul Haq , Abdullah-Al Jubayer , Md Mahmudul Islam , Asura Khanam Lisa , Biswanath Sikdar , Md. Enamul Haque
The white spot syndrome virus (WSSV), considered the deadliest pathogen impacting Penaeid shrimp (Penaeus monodon), remains worrisome for the global shrimp industry due to its extreme virulence and mortality rate of up to 100%. To date, there has been no breakthrough in effective antivirals or vaccines that can mitigate the financial damage caused by the pathogen. The distinctive structure of VP28 facilitates its role as a trimer, serving as the primary envelope protein of WSSV. It anchors to the viral envelope, directly interacts with PmRab7, a membrane protein in P. monodon, and aids in entry into the host. This research aims to discover antiviral drug candidates targeting VP28 trimer by screening a virtual library of 187 bioactive compounds derived from the medicinal herbs Azadirachta indica and Bacopa monnieri. To evaluate the drug ability of compounds in restricting VP28 trimer interaction within the endocytic pathway, a computational strategy was employed, including virtual screening, pharmacokinetics and toxicity analysis, and molecular dynamics (MD) simulation. The four strongest compounds, epicatechin, luteolin, kaempferol, and apigenin, exhibited binding affinities of −8.8, −8.8, −8.7, and −8.5 Kcal/mol, respectively, and demonstrated excellent pharmacokinetic properties. Furthermore, we employed 100 nanoseconds MD simulations and MM-PBSA binding free energy calculations to examine intermolecular interactions and confirmed the structural stability of the compounds at the VP28 binding site. The findings of this research suggest that these compounds hold promise in combating WSSV infection, reducing economic losses, and contributing to the sustainability of the shrimp industry.
{"title":"High-throughput screening of natural antiviral drug candidates against white spot syndrome virus targeting VP28 in Penaeus monodon: Computational drug design approaches","authors":"Md. Touki Tahamid Tusar ,&nbsp;Zubaer Hossen ,&nbsp;Hafizur Rahman Gazi ,&nbsp;Niamul Haq ,&nbsp;Abdullah-Al Jubayer ,&nbsp;Md Mahmudul Islam ,&nbsp;Asura Khanam Lisa ,&nbsp;Biswanath Sikdar ,&nbsp;Md. Enamul Haque","doi":"10.1016/j.jgeb.2024.100455","DOIUrl":"10.1016/j.jgeb.2024.100455","url":null,"abstract":"<div><div>The white spot syndrome virus (WSSV), considered the deadliest pathogen impacting Penaeid shrimp (<em>Penaeus monodon</em>), remains worrisome for the global shrimp industry due to its extreme virulence and mortality rate of up to 100%. To date, there has been no breakthrough in effective antivirals or vaccines that can mitigate the financial damage caused by the pathogen. The distinctive structure of VP28 facilitates its role as a trimer, serving as the primary envelope protein of WSSV. It anchors to the viral envelope, directly interacts with PmRab7, a membrane protein in <em>P. monodon</em>, and aids in entry into the host. This research aims to discover antiviral drug candidates targeting VP28 trimer by screening a virtual library of 187 bioactive compounds derived from the medicinal herbs <em>Azadirachta indica</em> and <em>Bacopa monnieri</em>. To evaluate the drug ability of compounds in restricting VP28 trimer interaction within the endocytic pathway, a computational strategy was employed, including virtual screening, pharmacokinetics and toxicity analysis, and molecular dynamics (MD) simulation. The four strongest compounds, epicatechin, luteolin, kaempferol, and apigenin, exhibited binding affinities of −8.8, −8.8, −8.7, and −8.5 Kcal/mol, respectively, and demonstrated excellent pharmacokinetic properties. Furthermore, we employed 100 nanoseconds MD simulations and MM-PBSA binding free energy calculations to examine intermolecular interactions and confirmed the structural stability of the compounds at the VP28 binding site. The findings of this research suggest that these compounds hold promise in combating WSSV infection, reducing economic losses, and contributing to the sustainability of the shrimp industry.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100455"},"PeriodicalIF":3.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploration of crucial stromal risk genes associated with prognostic significance and chemotherapeutic opportunities in invasive ductal breast carcinoma
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-24 DOI: 10.1016/j.jgeb.2024.100448
Guohua Tang , Zhi Wang , Wei Geng , Yang Yu , Yang Zhang

Background

Few studies revealed that stromal genes regulate the tumor microenvironment (TME). However, identification of key-risk genes in the invasive ductal breast carcinoma-associated stroma (IDBCS) and their associations with the prediction of risk group remains lacking.

Methods

This study used the GSE9014, GSE10797, GSE8977, GSE33692, and TGGA BRCA datasets. We explored the differentially expressed transcriptional markers, hub genes, gene modules, and enriched KEGG pathways. We employed a variety of algorithms, such as the log-rank test, the LASSO-cox model, the univariate regression model, and the multivariate regression model, to predict prognostic-risk genes and the prognostic-risk model. Finally, we employed a molecular docking-based study to explore the interaction of sensitive drugs with prognostic-risk genes.

Results

In comparing IDBCS and normal stroma, we discovered 1472 upregulated genes and 1400 downregulated genes (combined ES > 0585 and adjusted p-value < 0.05). The hub genes enrich cancer, immunity, and cellular signaling pathways. We explored the 12 key risk genes (ADAM8, CD86, CSRP1, DCTN2, EPHA1, GALNT10, IGFBP6, MIA, MMP11, RBM22, SLC39A4, and SYT2) in the IDBCS to identify the high-risk group and low-risk group patients. The high-risk group had a lower survival rate, and the constructed ROC curves evaluated the validity of the risk model. Expression validation and diagnostic efficacy revealed that the key stromal risk genes are consistently deregulated in the high-risk group and high stromal samples of the TCGA BRCA cohort. The expression of crucial risk genes, including CD86, CSRP1, EPHA1, GALNT10, IGFBP6, MIA, and RBM22 are associated with drug resistance and drug sensitivity. Finally, a molecular docking study explored several sensitive drugs (such as QL-XII-61, THZ-2-49, AZ628, NG-25, lapatinib, dasatinib, SB590885, and dabrafenib) interacted with these essential risk genes through hydrogen bonds and other chemical interactions.

Conclusions

Exploring essential prognostic-risk genes and their association with the prognosis, diagnostic efficacy, and risk-group prediction may provide substantial clues for targeting the breast cancer stromal key-risk genes.
{"title":"Exploration of crucial stromal risk genes associated with prognostic significance and chemotherapeutic opportunities in invasive ductal breast carcinoma","authors":"Guohua Tang ,&nbsp;Zhi Wang ,&nbsp;Wei Geng ,&nbsp;Yang Yu ,&nbsp;Yang Zhang","doi":"10.1016/j.jgeb.2024.100448","DOIUrl":"10.1016/j.jgeb.2024.100448","url":null,"abstract":"<div><h3>Background</h3><div>Few studies revealed that stromal genes regulate the tumor microenvironment (TME). However, identification of key-risk genes in the invasive ductal breast carcinoma-associated stroma (IDBCS) and their associations with the prediction of risk group remains lacking.</div></div><div><h3>Methods</h3><div>This study used the GSE9014, GSE10797, GSE8977, GSE33692, and TGGA BRCA datasets. We explored the differentially expressed transcriptional markers, hub genes, gene modules, and enriched KEGG pathways. We employed a variety of algorithms, such as the log-rank test, the LASSO-cox model, the univariate regression model, and the multivariate regression model, to predict prognostic-risk genes and the prognostic-risk model. Finally, we employed a molecular docking-based study to explore the interaction of sensitive drugs with prognostic-risk genes.</div></div><div><h3>Results</h3><div>In comparing IDBCS and normal stroma, we discovered 1472 upregulated genes and 1400 downregulated genes (combined ES &gt; 0585 and adjusted p-value &lt; 0.05). The hub genes enrich cancer, immunity, and cellular signaling pathways. We explored the 12 key risk genes (<em>ADAM8, CD86, CSRP1, DCTN2, EPHA1, GALNT10, IGFBP6, MIA, MMP11, RBM22, SLC39A4,</em> and <em>SYT2</em>) in the IDBCS to identify the high-risk group and low-risk group patients. The high-risk group had a lower survival rate, and the constructed ROC curves evaluated the validity of the risk model. Expression validation and diagnostic efficacy revealed that the key stromal risk genes are consistently deregulated in the high-risk group and high stromal samples of the TCGA BRCA cohort. The expression of crucial risk genes, including <em>CD86, CSRP1, EPHA1, GALNT10, IGFBP6, MIA,</em> and <em>RBM22</em> are associated with drug resistance and drug sensitivity. Finally, a molecular docking study explored several sensitive drugs (such as QL-XII-61, THZ-2-49, AZ628, NG-25, lapatinib, dasatinib, SB590885, and dabrafenib) interacted with these essential risk genes through hydrogen bonds and other chemical interactions.</div></div><div><h3>Conclusions</h3><div>Exploring essential prognostic-risk genes and their association with the prognosis, diagnostic efficacy, and risk-group prediction may provide substantial clues for targeting the breast cancer stromal key-risk genes.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100448"},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic analysis of Gobiopterus brachyopterus (Oxudercidae) from Grati Lake and The genus potential misidentification
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-24 DOI: 10.1016/j.jgeb.2024.100453
Septi Anitasari , Diana Arfiati , Susilo Susilo , Agung Pramana Warih Marhendra , Abdul Rahem Faqih , Akhsan Fikrillah Paricahya
The holotype of Gobiopterus brachyopterus originates from Grati Lake, Indonesia. It is locally called lempuk fish. The genus Gobiopterus has similar species, making identification difficult. A genetic study using the COI region revealed possible misidentification issues. Phylogenetic analysis showed that populations in India and Brunei are separate species. These populations formed distinct clades from the Grati Lake population. Genetic P-distance supported this, with a 21.7% difference for India and 21.9% for Brunei. A haplotype network confirmed the Grati Lake population’s uniqueness. It is genetically closer to Gobiopterus lacustris than to Indian or Brunei populations. G. brachyopterus was found to be genetically endemic to Grati Lake.
{"title":"Genetic analysis of Gobiopterus brachyopterus (Oxudercidae) from Grati Lake and The genus potential misidentification","authors":"Septi Anitasari ,&nbsp;Diana Arfiati ,&nbsp;Susilo Susilo ,&nbsp;Agung Pramana Warih Marhendra ,&nbsp;Abdul Rahem Faqih ,&nbsp;Akhsan Fikrillah Paricahya","doi":"10.1016/j.jgeb.2024.100453","DOIUrl":"10.1016/j.jgeb.2024.100453","url":null,"abstract":"<div><div>The holotype of <em>Gobiopterus brachyopterus</em> originates from Grati Lake, Indonesia. It is locally called lempuk fish. The genus <em>Gobiopterus</em> has similar species, making identification difficult. A genetic study using the COI region revealed possible misidentification issues. Phylogenetic analysis showed that populations in India and Brunei are separate species. These populations formed distinct clades from the Grati Lake population. Genetic P-distance supported this, with a 21.7% difference for India and 21.9% for Brunei. A haplotype network confirmed the Grati Lake population’s uniqueness. It is genetically closer to <em>Gobiopterus lacustris</em> than to Indian or Brunei populations. <em>G. brachyopterus</em> was found to be genetically endemic to Grati Lake.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100453"},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive evaluation of antibacterial and anticancer activities from indole butanoic acid
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-24 DOI: 10.1016/j.jgeb.2024.100452
Azhar H. Ali , Mohanad Yakdhan Saleh , Qusay Abdulazahra Yaqoob , Shakir M. Saied , Mohammed Sami Hasan , Khalid Ahmed Owaid , Basma A.A. Balboul , Heba.G. Abdelzaher , M.A. Abdelzaher , Alaa Muqbil Alsirhani
Focus of this study is on the use of the hydrazone compound (3) (N-(4-bromobenzylidene)-4-(1H-indol-3-yl) butane hydrazide), which was previously prepared from the reaction of the compound p-bromobenzaldehyde with the corresponding hydrazide (2), as an intermediate compound for the synthesis of azetidine, thiazolidine, tetrazole, oxadiazole and phthalazine heterocyclic compounds through its reaction with some cyclic reagents and catalysts such as chloro acetyl chloride, thioglycolic acid, sodium-azid, lead dioxide and Hydrogen chloride gas. The prepared compounds were characterized using physical properties and also spectroscopic methods such as infrared spectroscopy, nuclear magnetic resonance spectra of the proton and the isotope of carbon13 as well as mass spectrometry, which accurately identified the proposed structures of the prepared compounds. The identity of the prepared compounds was determined using physical and spectroscopic properties, where infrared and 1HNMR spectroscopy of the proton as well as carbon13 were used in addition to using mass spectrometry to verify the validity of the prepared structures. Conclusions: Also, the biological antibacterial evaluation of the compounds (4–8) was conducted and it gave a good result compared to the drug (8) used as a reference for the control, The MTT test was performed on the healthy and cancerous cells of the compounds (4,5,8) and gave an excellent result for the compound (8).
{"title":"Comprehensive evaluation of antibacterial and anticancer activities from indole butanoic acid","authors":"Azhar H. Ali ,&nbsp;Mohanad Yakdhan Saleh ,&nbsp;Qusay Abdulazahra Yaqoob ,&nbsp;Shakir M. Saied ,&nbsp;Mohammed Sami Hasan ,&nbsp;Khalid Ahmed Owaid ,&nbsp;Basma A.A. Balboul ,&nbsp;Heba.G. Abdelzaher ,&nbsp;M.A. Abdelzaher ,&nbsp;Alaa Muqbil Alsirhani","doi":"10.1016/j.jgeb.2024.100452","DOIUrl":"10.1016/j.jgeb.2024.100452","url":null,"abstract":"<div><div>Focus of this study is on the use of the hydrazone compound (3) (N-(4-bromobenzylidene)-4-(1H-indol-3-yl) butane hydrazide), which was previously prepared from the reaction of the compound p-bromobenzaldehyde with the corresponding hydrazide (2), as an intermediate compound for the synthesis of azetidine, thiazolidine, tetrazole, oxadiazole and phthalazine heterocyclic compounds through its reaction with some cyclic reagents and catalysts such as chloro acetyl chloride, thioglycolic acid, sodium-azid, lead dioxide and Hydrogen chloride gas. The prepared compounds were characterized using physical properties and also spectroscopic methods such as infrared spectroscopy, nuclear magnetic resonance spectra of the proton and the isotope of carbon<sup>13</sup> as well as mass spectrometry, which accurately identified the proposed structures of the prepared compounds. The identity of the prepared compounds was determined using physical and spectroscopic properties, where infrared and <sup>1</sup>HNMR spectroscopy of the proton as well as carbon<sup>13</sup> were used in addition to using mass spectrometry to verify the validity of the prepared structures. Conclusions: Also, the biological antibacterial evaluation of the compounds (4–8) was conducted and it gave a good result compared to the drug (8) used as a reference for the control, The MTT test was performed on the healthy and cancerous cells of the compounds (4,5,8) and gave an excellent result for the compound (8).</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100452"},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Genetic Engineering and Biotechnology
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