Pub Date : 2025-01-01DOI: 10.1016/j.biochi.2024.08.012
Daria A. Dmitrieva , Olga A. Belozerova , Alexey V. Mishin , Ilia V. Yampolsky , Alexey A. Kotlobay
Among nearly a hundred known bioluminescent systems, only about a dozen have been studied to some extent, and the structures of only a few luciferins have been established. Moreover, the biosynthesis pathway is known only for two of them - the fungal and bacterial ones. Marine polychaetes of the Odontosyllis genus possess bright bioluminescence. The structures of its bioluminescence system key components were recently elucidated, and a possible pathway of the luciferin biosynthesis was proposed. Here we report the transaminase enzyme from Odontosyllis undecimdonta, the first potential participant of the cascade. We demonstrate that the discovered ferment catalyzes the transamination of the cys2DOPA, one of the potential luciferin biosynthetic precursors. The results of the experiments support the hypothesis that the discovered enzyme might be the part of the Odontosyllis luciferin biosynthesis pathway.
{"title":"New transaminase from Odontosyllis undecimdonta the first potential enzyme of the luciferin biosynthesis pathway","authors":"Daria A. Dmitrieva , Olga A. Belozerova , Alexey V. Mishin , Ilia V. Yampolsky , Alexey A. Kotlobay","doi":"10.1016/j.biochi.2024.08.012","DOIUrl":"10.1016/j.biochi.2024.08.012","url":null,"abstract":"<div><div>Among nearly a hundred known bioluminescent systems, only about a dozen have been studied to some extent, and the structures of only a few luciferins have been established. Moreover, the biosynthesis pathway is known only for two of them - the fungal and bacterial ones. Marine polychaetes of the <em>Odontosyllis</em> genus possess bright bioluminescence. The structures of its bioluminescence system key components were recently elucidated, and a possible pathway of the luciferin biosynthesis was proposed. Here we report the transaminase enzyme from <em>Odontosyllis undecimdonta</em>, the first potential participant of the cascade. We demonstrate that the discovered ferment catalyzes the transamination of the cys2DOPA, one of the potential luciferin biosynthetic precursors. The results of the experiments support the hypothesis that the discovered enzyme might be the part of the <em>Odontosyllis</em> luciferin biosynthesis pathway.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 82-88"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
There is a great need for novel approaches to the treatment of epithelial ovarian carcinoma, which is the leading cause of mortality from gynecological malignancies. In this study, the pre-targeting technology was used to enhance the in vivo targeting of cytotoxic module composed of nanoliposomes loaded with a truncated form of Pseudomonas aeruginosa exotoxin A (PE40) to cancer cells. Pre-targeting system used in this study is composed of bacterial ribonuclease Barnase and its natural antitoxin Barstar. Barstar, genetically fused to various engineered scaffold proteins specific to tumor-associated antigens (HER2, EpCAM) serves as a primary module for precise cancer cell recognition. Barnase conjugated to a therapeutic agent serves as a cytotoxic or secondary module for malignant cell elimination. Due to strong non-covalent interaction (KD10−14 M) of Barstar and Barnase, the primary and secondary modules efficiently interact with each other on the cell surface, which has been proven by confocal microscopy and flow cytometry. Using mice with SKOV-3 ovarian cancer xenografts, we have shown that regardless of the targeting module, the pre-targeting approach is much more effective than a single-step active targeting.
{"title":"The Barnase-Barstar-based pre-targeting strategy for enhanced antitumor therapy in vivo","authors":"G.M. Proshkina , E.I. Shramova , A.B. Mirkasyimov , O. Yu Griaznova , E.V. Konovalova , A.A. Schulga , S.M. Deyev","doi":"10.1016/j.biochi.2024.09.011","DOIUrl":"10.1016/j.biochi.2024.09.011","url":null,"abstract":"<div><div>There is a great need for novel approaches to the treatment of epithelial ovarian carcinoma, which is the leading cause of mortality from gynecological malignancies. In this study, the pre-targeting technology was used to enhance the <em>in vivo</em> targeting of cytotoxic module composed of nanoliposomes loaded with a truncated form of <em>Pseudomonas aeruginosa</em> exotoxin A (PE40) to cancer cells. Pre-targeting system used in this study is composed of bacterial ribonuclease Barnase and its natural antitoxin Barstar. Barstar, genetically fused to various engineered scaffold proteins specific to tumor-associated antigens (HER2, EpCAM) serves as a primary module for precise cancer cell recognition. Barnase conjugated to a therapeutic agent serves as a cytotoxic or secondary module for malignant cell elimination. Due to strong non-covalent interaction (K<sub>D</sub>10<sup>−14</sup> M) of Barstar and Barnase, the primary and secondary modules efficiently interact with each other on the cell surface, which has been proven by confocal microscopy and flow cytometry. Using mice with SKOV-3 ovarian cancer xenografts, we have shown that regardless of the targeting module, the pre-targeting approach is much more effective than a single-step active targeting.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 158-166"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.biochi.2024.08.005
Sunil Pani , Unmod Senapati , Bijayashree Sahu , Benudhara Pati , Gourabamani Swalsingh , Punyadhara Pani , Birendra Kumar Bindhani , K Gopinath Achary , Naresh C. Bal
In mammals, skeletal muscles (SkMs) and adipose tissues regulate energy homeostasis and share developmental origins. Notably, the perirenal adipose tissue (PRAT) depot has been reported to display adipocyte heterogeneity: while some originated from Myogenic factor 5 (Myf-5) expressing progenitors, others did not. Our study examines the expression and distribution of Myf-5 using immunohistochemical staining and western blotting of PRAT, gastrocnemius, and trapezius from goat at various developmental stages. Contrary to earlier beliefs, functionally divergent SkM gastrocnemius and trapezius showed similar Myf-5 expressional pattern. SkM abundantly expresses Myf-5 in developing myocytes which gradually becomes limited to the nucleus of myogenic stem cells and is retained only in a few differentiated postnatal fibers. During the same period, PRAT displays a unique brown-to-white transition. PRAT exhibited an elevated expression of Myf-5 during prenatal periods, which declines thereafter and becomes negligible during adulthood where it gets fully enriched white adipocytes. The reduction of Myf-5 during the neonatal period was common to all three tissues. However, Myf-5 expression was retained in some of the differentiated myofibers while it was undetectable in adult PRAT. These observations suggest a possible developmental interplay between adipose tissue and SkM where Myf-5 might be a major regulator.
在哺乳动物中，骨骼肌（SkMs）和脂肪组织调节能量平衡，并且具有共同的发育起源。值得注意的是，有报道称肾周脂肪组织（PRAT）库显示出脂肪细胞的异质性：一些来源于表达肌原因子 5（Myf-5）的祖细胞，而另一些则不是。我们的研究采用免疫组化染色和 Western 印迹法对处于不同发育阶段的山羊 PRAT、腓肠肌和斜方肌进行了研究，探讨了 Myf-5 的表达和分布情况。与之前的观点相反，功能上不同的SkM腓肠肌和斜方肌表现出相似的Myf-5表达模式。SkM在发育中的肌细胞中大量表达Myf-5，而Myf-5逐渐局限于成肌干细胞的细胞核中，仅保留在少数分化后的纤维中。在同一时期，PRAT 表现出独特的棕色到白色的转变。PRAT在产前表现出Myf-5的表达升高，随后下降，到成年期可忽略不计，在成年期Myf-5完全富集到白色脂肪细胞中。新生儿期 Myf-5 的减少是所有三种组织的共同特征。然而，在一些已分化的肌纤维中保留了Myf-5的表达，而在成年PRAT中则检测不到。这些观察结果表明，脂肪组织和SkM之间可能存在发育上的相互作用，其中Myf-5可能是一个主要的调节因子。
{"title":"Developmental overlap between skeletal muscle maturation and perirenal fat brown-to-white transition in goats: Exploring the role of Myf-5","authors":"Sunil Pani , Unmod Senapati , Bijayashree Sahu , Benudhara Pati , Gourabamani Swalsingh , Punyadhara Pani , Birendra Kumar Bindhani , K Gopinath Achary , Naresh C. Bal","doi":"10.1016/j.biochi.2024.08.005","DOIUrl":"10.1016/j.biochi.2024.08.005","url":null,"abstract":"<div><div>In mammals, skeletal muscles (SkMs) and adipose tissues regulate energy homeostasis and share developmental origins. Notably, the perirenal adipose tissue (PRAT) depot has been reported to display adipocyte heterogeneity: while some originated from Myogenic factor 5 (Myf-5) expressing progenitors, others did not. Our study examines the expression and distribution of Myf-5 using immunohistochemical staining and western blotting of PRAT, gastrocnemius, and trapezius from goat at various developmental stages. Contrary to earlier beliefs, functionally divergent SkM gastrocnemius and trapezius showed similar Myf-5 expressional pattern. SkM abundantly expresses Myf-5 in developing myocytes which gradually becomes limited to the nucleus of myogenic stem cells and is retained only in a few differentiated postnatal fibers. During the same period, PRAT displays a unique brown-to-white transition. PRAT exhibited an elevated expression of Myf-5 during prenatal periods, which declines thereafter and becomes negligible during adulthood where it gets fully enriched white adipocytes. The reduction of Myf-5 during the neonatal period was common to all three tissues. However, Myf-5 expression was retained in some of the differentiated myofibers while it was undetectable in adult PRAT. These observations suggest a possible developmental interplay between adipose tissue and SkM where Myf-5 might be a major regulator.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 1-7"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.biochi.2024.08.008
Swati Lamba, Priyanka Mazire, Amit Roy
Unicellular protozoan parasite Leishmania donovani is the causative agent for visceral leishmaniasis (VL) or Kala-azar, a neglected fatal parasitic disease. The conventional treatment of VL consists of therapeutic agents having several shortcomings such as toxicity, high cost, efficacy variance and increased drug resistance. Therefore, there is a desperate need to develop an effective treatment against the parasite. Previous reports suggested that flavonoids can inhibit the enzyme Leishmania donovani DNA topoisomerase I (LdTopILS). Therefore, for the first time in this present study, we divulge HSP (one of the natural sources of flavonoids), as a potent natural antileishmanial compound with efficacy in BALB/c mice at 20 mg/kg of body weight, inhibits LdTopILS at 97 % of its activity at 160 μM in preincubation condition (competitively). It binds with free enzyme and does not allow it to bind with the substrate DNA. Moreover, HSP does not stabilize DNA-topoisomerase I cleavable complex. Thus, HSP acts a catalytic topoisomerase I inhibitor, which inhibits complete activity by binding with Lys269 and Thr411 of large subunit of the enzyme. On the other hand, HSP induces the topo I-mediated programmed cell death process by the formation of cellular reactive oxygen species, resulting in depolarization of mitochondrial membrane potential, followed by fragmentation of nuclear DNA. Therefore, the present study illuminates a natural flavonoid that in future might be a promising lead for the treatment of VL.
单细胞原生动物利什曼原虫（Leishmania donovani）是内脏利什曼病（VL）或卡拉扎病（Kala-azar）的病原体，这是一种被忽视的致命寄生虫病。内脏利什曼病的传统治疗方法包括使用具有毒性、高成本、疗效不一和耐药性增加等缺点的治疗药物。因此，迫切需要开发一种有效的寄生虫治疗方法。以前的报道表明，黄酮类化合物能抑制唐氏利什曼原虫 DNA 拓扑异构酶 I（LdTopILS）。因此，在本研究中，我们首次发现 HSP（黄酮类化合物的天然来源之一）是一种有效的天然抗利什曼病化合物，对 BALB/c 小鼠的疗效为 20 毫克/千克体重，在预孵育条件下 160 μM 时可抑制 LdTopILS 97% 的活性（竞争性）。它与游离酶结合，不允许其与底物 DNA 结合。此外，HSP 不会稳定 DNA-拓扑异构酶 I 可裂解复合物。因此，HSP 是一种催化拓扑异构酶 I 抑制剂，它通过与酶大亚基的 Lys269 和 Thr411 结合来抑制拓扑异构酶 I 的全部活性。另一方面，HSP 通过形成细胞活性氧，诱导拓扑异构酶 I 介导的细胞程序性死亡过程，导致线粒体膜电位去极化，继而导致核 DNA 断裂。因此，本研究揭示了一种天然黄酮类化合物，它将来可能成为治疗 VL 的一种有前途的线索。
{"title":"Unveiling the mechanism of hesperidin-induced LdTopI-mediated cell death pathway in protozoan parasite Leishmania donovani","authors":"Swati Lamba, Priyanka Mazire, Amit Roy","doi":"10.1016/j.biochi.2024.08.008","DOIUrl":"10.1016/j.biochi.2024.08.008","url":null,"abstract":"<div><div>Unicellular protozoan parasite <em>Leishmania donovani</em> is the causative agent for visceral leishmaniasis (VL) or Kala-azar, a neglected fatal parasitic disease. The conventional treatment of VL consists of therapeutic agents having several shortcomings such as toxicity, high cost, efficacy variance and increased drug resistance. Therefore, there is a desperate need to develop an effective treatment against the parasite. Previous reports suggested that flavonoids can inhibit the enzyme <em>Leishmania donovani</em> DNA topoisomerase I (LdTopILS). Therefore, for the first time in this present study, we divulge HSP (one of the natural sources of flavonoids), as a potent natural antileishmanial compound with efficacy in BALB/c mice at 20 mg/kg of body weight, inhibits LdTopILS at 97 % of its activity at 160 μM in preincubation condition (competitively). It binds with free enzyme and does not allow it to bind with the substrate DNA. Moreover, HSP does not stabilize DNA-topoisomerase I cleavable complex. Thus, HSP acts a catalytic topoisomerase I inhibitor, which inhibits complete activity by binding with Lys269 and Thr411 of large subunit of the enzyme. On the other hand, HSP induces the topo I-mediated programmed cell death process by the formation of cellular reactive oxygen species, resulting in depolarization of mitochondrial membrane potential, followed by fragmentation of nuclear DNA. Therefore, the present study illuminates a natural flavonoid that in future might be a promising lead for the treatment of VL.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 15-31"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.biochi.2024.09.013
Yongpeng Fu, Jeroen De Buck
The split trehalase biosensor has potential as a versatile diagnostic technology. Split enzymes are engineered proteins, divided into inactive fragments, which can reassemble and regain activity when brought together by an analyte. The split TreA biosensor requires no sample processing and produces stable signals (in the form of glucose). Split trehalase reagents can function in blood, but periplasmic trehalase of E. coli requires blood acidification for maximal activity. The objective of this study was to obtain split trehalase with near physiological pH optimum. For this purpose, periplasmic trehalases of Cellvibrio spp. with higher activity at neutral pH, were split in analogy with the E. coli TreA into hood and catalytic domains. However, these split trehalases displayed self-complementation due to spontaneous reassembly. In contrast, when catalytic domains of Cellvibrio trehalases were combined with E. coli hood domains, these hybrids displayed conditional complementation capacity when split trehalase fragments fused to immunoglobulin-binding protein G (STIGA) were used to quantify immunoglobulin concentrations. Other hybrid combinations of Cellvibrio spp. had increased activity compared to the cognate pairs, albeit with strong self-complementation. A mutagenesis analysis of residues responsible for self-complementation led to uncoupling of self-complementation from allostery. The Michaelis-Menten kinetics of Cellvibrio enzymes and fragment pairs confirmed improved activity of a mutated hybrid pair of Cellvibrio hood and catalytic domains at physiological pH. In conclusion, the improvements in pH optimum and activity, demonstrated with STIGA, can now be leveraged to enhance other variations of the split trehalase biosensor platform, broadening its utility for testing clinical samples.
{"title":"Enhanced activity of split trehalase biosensors by interspecies domain combineering","authors":"Yongpeng Fu, Jeroen De Buck","doi":"10.1016/j.biochi.2024.09.013","DOIUrl":"10.1016/j.biochi.2024.09.013","url":null,"abstract":"<div><div>The split trehalase biosensor has potential as a versatile diagnostic technology. Split enzymes are engineered proteins, divided into inactive fragments, which can reassemble and regain activity when brought together by an analyte. The split TreA biosensor requires no sample processing and produces stable signals (in the form of glucose). Split trehalase reagents can function in blood, but periplasmic trehalase of <em>E. coli</em> requires blood acidification for maximal activity. The objective of this study was to obtain split trehalase with near physiological pH optimum. For this purpose, periplasmic trehalases of <em>Cellvibrio</em> spp. with higher activity at neutral pH, were split in analogy with the <em>E</em>. <em>coli</em> TreA into hood and catalytic domains. However, these split trehalases displayed self-complementation due to spontaneous reassembly. In contrast, when catalytic domains of <em>Cellvibrio</em> trehalases were combined with <em>E. coli</em> hood domains, these hybrids displayed conditional complementation capacity when split trehalase fragments fused to immunoglobulin-binding protein G (STIGA) were used to quantify immunoglobulin concentrations. Other hybrid combinations of <em>Cellvibrio</em> spp. had increased activity compared to the cognate pairs, albeit with strong self-complementation. A mutagenesis analysis of residues responsible for self-complementation led to uncoupling of self-complementation from allostery. The Michaelis-Menten kinetics of <em>Cellvibrio</em> enzymes and fragment pairs confirmed improved activity of a mutated hybrid pair of <em>Cellvibrio</em> hood and catalytic domains at physiological pH. In conclusion, the improvements in pH optimum and activity, demonstrated with STIGA, can now be leveraged to enhance other variations of the split trehalase biosensor platform, broadening its utility for testing clinical samples.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 167-175"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natural products are widely used in different aspects of our lives – from household cleaners and food production, via cosmetics and aromatherapy, to both alternative and traditional medicine. In our research group, we have recently described several monoterpenoids with potential in the antiviral and anticancer therapy by allosteric targeting of aryl hydrocarbon receptor (AhR). Prior to any practical application, biological effects on human organism must be taken in concern. This review article is focused on the biological effects of 5 monoterpenoids on the human health previously identified as AhR antagonists with a therapeutic potential as antiviral and anticancer agents. We have thoroughly described cytotoxic, anti-inflammatory, anti-proliferative, and anticancer effects, as well as known interactions with nuclear receptors. As clearly demonstrated, monoterpenoids in general represent almost an inexhaustible reservoir of natural compounds possessing the ability to influence, modulate and improve human health.
{"title":"Dietary monoterpenoids and human health: Unlocking the potential for therapeutic use","authors":"Barbora Vyhlídalová , Karolína Ondrová , Iveta Zůvalová","doi":"10.1016/j.biochi.2024.09.002","DOIUrl":"10.1016/j.biochi.2024.09.002","url":null,"abstract":"<div><div>Natural products are widely used in different aspects of our lives – from household cleaners and food production, via cosmetics and aromatherapy, to both alternative and traditional medicine. In our research group, we have recently described several monoterpenoids with potential in the antiviral and anticancer therapy by allosteric targeting of aryl hydrocarbon receptor (AhR). Prior to any practical application, biological effects on human organism must be taken in concern. This review article is focused on the biological effects of 5 monoterpenoids on the human health previously identified as AhR antagonists with a therapeutic potential as antiviral and anticancer agents. We have thoroughly described cytotoxic, anti-inflammatory, anti-proliferative, and anticancer effects, as well as known interactions with nuclear receptors. As clearly demonstrated, monoterpenoids in general represent almost an inexhaustible reservoir of natural compounds possessing the ability to influence, modulate and improve human health.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 89-100"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.biochi.2024.08.007
Jyoti Sankar Prusty, Awanish Kumar
Mycoses infect millions of people annually across the world. The most common mycosis agent, Candida albicans is responsible for a great deal of illness and death. C. albicans infection is becoming more widespread and the current antifungals polyenes, triazoles, and echinocandins are less efficient against it. Investigating antifungal peptides (AFPs) as therapeutic is gaining momentum. Therefore, we used MALDI-TOF/MS analysis to identify AFPs and protein-protein docking to analyze their interactions with the C. albicans target protein. Some microorganisms with strong antifungal action against C. albicans were selected for the isolation of AFPs. Using MALDI-TOF/MS, we identified 3 AFPs Chitin binding protein (ACW83017.1; Bacillus licheniformis), the bifunctional protein GlmU (BBQ13478.1; Stenotrophomonas maltophilia), and zinc metalloproteinase aureolysin (BBA25172.1; Staphylococcus aureus). These AFPs showed robust interactions with C. albicans target protein Sap5. We deciphered some important residues in identified APFs and highlighted interaction with Sap5 through hydrogen bonds, protein-protein interactions, and salt bridges using protein-protein docking and MD simulations. The three discovered AFPs-Sap5 complexes exhibit different levels of stability, as seen by the RMSD analysis and interaction patterns. Among protein-protein interactions, the remarkable stability of the BBQ25172.1-2QZX complex highlights the role of salt bridges and hydrogen bonds. Identified AFPs could be further studied for developing successful antifungal candidates and peptide-based new antifungal therapeutic strategies as fresh insights into addressing antifungal resistance also.
{"title":"In silico-driven identification and experimental confirmation of antifungal proteins (AFPs) against Candida albicans","authors":"Jyoti Sankar Prusty, Awanish Kumar","doi":"10.1016/j.biochi.2024.08.007","DOIUrl":"10.1016/j.biochi.2024.08.007","url":null,"abstract":"<div><div>Mycoses infect millions of people annually across the world. The most common mycosis agent, <em>Candida albicans</em> is responsible for a great deal of illness and death. <em>C. albicans</em> infection is becoming more widespread and the current antifungals polyenes, triazoles, and echinocandins are less efficient against it. Investigating antifungal peptides (AFPs) as therapeutic is gaining momentum. Therefore, we used MALDI-TOF/MS analysis to identify AFPs and protein-protein docking to analyze their interactions with the <em>C. albicans</em> target protein. Some microorganisms with strong antifungal action against <em>C</em>. <em>albicans</em> were selected for the isolation of AFPs. Using MALDI-TOF/MS, we identified 3 AFPs Chitin binding protein (ACW83017.1; <em>Bacillus licheniformis</em>), the bifunctional protein GlmU (BBQ13478.1; <em>Stenotrophomonas maltophilia</em>), and zinc metalloproteinase aureolysin (BBA25172.1; Staphylococcus aureus). These AFPs showed robust interactions with <em>C. albicans</em> target protein Sap5. We deciphered some important residues in identified APFs and highlighted interaction with Sap5 through hydrogen bonds, protein-protein interactions, and salt bridges using protein-protein docking and MD simulations. The three discovered AFPs-Sap5 complexes exhibit different levels of stability, as seen by the RMSD analysis and interaction patterns. Among protein-protein interactions, the remarkable stability of the BBQ25172.1-2QZX complex highlights the role of salt bridges and hydrogen bonds. Identified AFPs could be further studied for developing successful antifungal candidates and peptide-based new antifungal therapeutic strategies as fresh insights into addressing antifungal resistance also.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 44-57"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.biochi.2024.08.006
Shengjie Yan, Meng Zhan, Zhi Liu, Xianwen Zhang
Proline biosynthesis and catabolism pathways are executed by powerful action of specific enzymes that are subjected to environmental fluctuations at the transcriptional level. Previous researches have demonstrated that osmotic stress-induced upstream events can affect the expression of proline metabolism-related genes, which results in adjustable free proline accumulation to protect plant cells from severe damage. Here, we mainly describe the mechanisms for how some key factors, such as transcription factors, ABA (abscisic acid), Ca2+, MAPK cascades, CK (cytokinin) and phospholipase, in a phosphorylated manner, vividly function in the transcriptional regulation of proline metabolism under osmotic stress. These mechanisms reveal that sustaining of proline homeostasis is an efficient way for plants to adapt to osmotic stress.
{"title":"Insight into the transcriptional regulation of key genes involved in proline metabolism in plants under osmotic stress","authors":"Shengjie Yan, Meng Zhan, Zhi Liu, Xianwen Zhang","doi":"10.1016/j.biochi.2024.08.006","DOIUrl":"10.1016/j.biochi.2024.08.006","url":null,"abstract":"<div><div>Proline biosynthesis and catabolism pathways are executed by powerful action of specific enzymes that are subjected to environmental fluctuations at the transcriptional level. Previous researches have demonstrated that osmotic stress-induced upstream events can affect the expression of proline metabolism-related genes, which results in adjustable free proline accumulation to protect plant cells from severe damage. Here, we mainly describe the mechanisms for how some key factors, such as transcription factors, ABA (abscisic acid), Ca<sup>2+</sup>, MAPK cascades, CK (cytokinin) and phospholipase, in a phosphorylated manner, vividly function in the transcriptional regulation of proline metabolism under osmotic stress. These mechanisms reveal that sustaining of proline homeostasis is an efficient way for plants to adapt to osmotic stress.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 8-14"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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