Pub Date : 2024-03-23DOI: 10.1007/s12104-024-10166-6
Neelam, Himanshu Singh
In preparation for a detailed exploration of the structural and functional aspects of the Ser2Ala mutant of human carbonic anhydrase II, we present here almost complete sequence-specific resonance assignments for 1H, 15N, and 13C. The mutation of serine to alanine at position 2, located in the N-terminal region of the enzyme, significantly alters the hydrophilic nature of the site, rendering it hydrophobic. Consequently, there is an underlying assumption that this mutation would repel water from the site. However, intriguingly, comparative analysis of the mutant structure with the wild type reveals minimal discernible differences. These assignments serve as the basis for in-depth studies on histidine dynamics, protonation states, and its intricate role in protein-water interactions and catalysis.
为了准备对人类碳酸酐酶 II 的 Ser2Ala 突变体的结构和功能方面进行详细的探索,我们在此提供了几乎完整的 1H、15N 和 13C 序列特异性共振赋值。位于酶 N 端区域的第 2 位丝氨酸突变为丙氨酸,大大改变了该位点的亲水性,使其成为疏水性位点。因此,有一种基本假设认为,这种突变会使该位点拒水。然而,有趣的是,对突变体结构与野生型结构的比较分析显示,两者之间的差异微乎其微。这些结果为深入研究组氨酸动力学、质子化状态及其在蛋白质与水的相互作用和催化作用中的复杂作用奠定了基础。
{"title":"1H, 15N and13C resonance assignments of S2A mutant of human carbonic anhydrase II","authors":"Neelam, Himanshu Singh","doi":"10.1007/s12104-024-10166-6","DOIUrl":"10.1007/s12104-024-10166-6","url":null,"abstract":"<div><p>In preparation for a detailed exploration of the structural and functional aspects of the Ser2Ala mutant of human carbonic anhydrase II, we present here almost complete sequence-specific resonance assignments for <sup>1</sup>H, <sup>15</sup>N, and <sup>13</sup>C. The mutation of serine to alanine at position 2, located in the N-terminal region of the enzyme, significantly alters the hydrophilic nature of the site, rendering it hydrophobic. Consequently, there is an underlying assumption that this mutation would repel water from the site. However, intriguingly, comparative analysis of the mutant structure with the wild type reveals minimal discernible differences. These assignments serve as the basis for in-depth studies on histidine dynamics, protonation states, and its intricate role in protein-water interactions and catalysis.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"45 - 49"},"PeriodicalIF":0.8,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-12DOI: 10.1007/s12104-024-10165-7
Maya J. Pandya, Wojciech Augustyniak, Matthew J. Cliff, Ilka Lindner, Anne Stinn, Jan Kahmann, Koen Temmerman, Hugh R. W. Dannatt, Jonathan P. Waltho, Martin J. Watson
The backbone 1H, 13C and 15N resonance assignment of Ubiquitin Specific Protease 7 catalytic domain (residues 208–554) was performed in its complex with a small molecule ligand and in its apo form as a reference. The amide 1H-15N signal intensities were boosted by an amide hydrogen exchange protocol, where expressed 2H, 13C, 15N-labeled protein was unfolded and re-folded to ensure exchange of amide deuterons to protons. The resonance assignments were used to determine chemical shift perturbations on ligand binding, which are consistent with the binding site observed by crystallography.
{"title":"Backbone 1H, 13C and 15N resonance assignment of the ubiquitin specific protease 7 catalytic domain (residues 208–554) in complex with a small molecule ligand","authors":"Maya J. Pandya, Wojciech Augustyniak, Matthew J. Cliff, Ilka Lindner, Anne Stinn, Jan Kahmann, Koen Temmerman, Hugh R. W. Dannatt, Jonathan P. Waltho, Martin J. Watson","doi":"10.1007/s12104-024-10165-7","DOIUrl":"10.1007/s12104-024-10165-7","url":null,"abstract":"<div><p>The backbone <sup>1</sup>H, <sup>13</sup>C and <sup>15</sup>N resonance assignment of Ubiquitin Specific Protease 7 catalytic domain (residues 208–554) was performed in its complex with a small molecule ligand and in its <i>apo</i> form as a reference. The amide <sup>1</sup>H-<sup>15</sup>N signal intensities were boosted by an amide hydrogen exchange protocol, where expressed <sup>2</sup>H, <sup>13</sup>C, <sup>15</sup>N-labeled protein was unfolded and re-folded to ensure exchange of amide deuterons to protons. The resonance assignments were used to determine chemical shift perturbations on ligand binding, which are consistent with the binding site observed by crystallography.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"33 - 44"},"PeriodicalIF":0.8,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-11DOI: 10.1007/s12104-024-10167-5
Bikash R. Sahoo, Vivekanandan Subramanian, James C.A. Bardwell
Human small EDRK-rich factor protein SERF2 is a cellular driver of protein amyloid formation, a process that has been linked to neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. SERF2 is a 59 amino acid protein, highly charged, and well conserved whose structure and physiological function is unclear. SERF family proteins including human SERF2 have shown a tendency to form fuzzy complexes with misfolded proteins such as α-Synuclein which has been linked to Parkinson’s disease. SERF family proteins have been recently identified to bind nucleic acids, but the binding mechanism(s) remain enigmatic. Here, using multidimensional solution NMR, we report the 1H, 15N, and 13C chemical shift assignments (~ 86% of backbone resonance assignments) for human SERF2. TALOS-N predicted secondary structure of SERF2 showed three very short helices (3–4 residues long) in the N-terminal region of the protein and a long helix in the C-terminal region spanning residues 37–46 which is consistent with the helical content indicated by circular dichroism spectroscopy. Paramagnetic relaxation enhancement NMR analysis revealed that a short C-terminal region E53-K55 is in the proximity of the N-terminus. Having the backbone assignment of SERF2 allowed us to probe its interaction with α-Synuclein and to identify the residues in SERF2 binding interfaces that likely promote α-Synuclein aggregation.
{"title":"Backbone 1H, 13C, and 15N chemical shift assignments for human SERF2","authors":"Bikash R. Sahoo, Vivekanandan Subramanian, James C.A. Bardwell","doi":"10.1007/s12104-024-10167-5","DOIUrl":"10.1007/s12104-024-10167-5","url":null,"abstract":"<div><p>Human small EDRK-rich factor protein SERF2 is a cellular driver of protein amyloid formation, a process that has been linked to neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. SERF2 is a 59 amino acid protein, highly charged, and well conserved whose structure and physiological function is unclear. SERF family proteins including human SERF2 have shown a tendency to form fuzzy complexes with misfolded proteins such as α-Synuclein which has been linked to Parkinson’s disease. SERF family proteins have been recently identified to bind nucleic acids, but the binding mechanism(s) remain enigmatic. Here, using multidimensional solution NMR, we report the <sup>1</sup>H, <sup>15</sup>N, and <sup>13</sup>C chemical shift assignments (~ 86% of backbone resonance assignments) for human SERF2. TALOS-N predicted secondary structure of SERF2 showed three very short helices (3–4 residues long) in the N-terminal region of the protein and a long helix in the C-terminal region spanning residues 37–46 which is consistent with the helical content indicated by circular dichroism spectroscopy. Paramagnetic relaxation enhancement NMR analysis revealed that a short C-terminal region E53-K55 is in the proximity of the N-terminus. Having the backbone assignment of SERF2 allowed us to probe its interaction with α-Synuclein and to identify the residues in SERF2 binding interfaces that likely promote α-Synuclein aggregation.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"51 - 57"},"PeriodicalIF":0.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140099982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-07DOI: 10.1007/s12104-024-10163-9
Patryk Ludzia, Hanako Hayashi, Timothy Robinson, Bungo Akiyoshi, Christina Redfield
KKT4 is a multi-domain kinetochore protein specific to kinetoplastids, such as Trypanosoma brucei. It lacks significant sequence similarity to known kinetochore proteins in other eukaryotes. Our recent X-ray structure of the C-terminal region of KKT4 shows that it has a tandem BRCT (BRCA1 C Terminus) domain fold with a sulfate ion bound in a typical binding site for a phosphorylated serine or threonine. Here we present the 1H, 13C and 15N resonance assignments for the BRCT domain of KKT4 (KKT4463–645) from T. brucei. We show that the BRCT domain can bind phosphate ions in solution using residues involved in sulfate ion binding in the X-ray structure. We have used these assignments to characterise the secondary structure and backbone dynamics of the BRCT domain in solution. Mutating the residues involved in phosphate ion binding in T. brucei KKT4 BRCT results in growth defects confirming the importance of the BRCT phosphopeptide-binding activity in vivo. These results may facilitate rational drug design efforts in the future to combat diseases caused by kinetoplastid parasites.
KKT4 是一种多域动核蛋白,专属于动核细胞,如布氏锥虫。它与其他真核生物的已知动核蛋白缺乏明显的序列相似性。我们最近对 KKT4 C 端区域的 X 射线结构显示,它有一个串联的 BRCT(BRCA1 C Terminus)结构域折叠,硫酸根离子与磷酸化丝氨酸或苏氨酸的典型结合位点结合。在这里,我们介绍了布鲁氏菌 KKT4(KKT4463-645)BRCT 结构域的 1H、13C 和 15N 共振分配。我们利用 X 射线结构中参与硫酸根离子结合的残基,证明 BRCT 结构域能在溶液中结合磷酸根离子。我们利用这些分配来描述 BRCT 结构域在溶液中的二级结构和骨架动力学特征。突变布鲁氏菌 KKT4 BRCT 中参与磷酸盐离子结合的残基会导致生长缺陷,这证实了 BRCT 磷肽结合活性在体内的重要性。这些结果可能有助于未来的合理药物设计工作,以防治由内生寄生虫引起的疾病。
{"title":"NMR study of the structure and dynamics of the BRCT domain from the kinetochore protein KKT4","authors":"Patryk Ludzia, Hanako Hayashi, Timothy Robinson, Bungo Akiyoshi, Christina Redfield","doi":"10.1007/s12104-024-10163-9","DOIUrl":"10.1007/s12104-024-10163-9","url":null,"abstract":"<div><p>KKT4 is a multi-domain kinetochore protein specific to kinetoplastids, such as <i>Trypanosoma brucei</i>. It lacks significant sequence similarity to known kinetochore proteins in other eukaryotes. Our recent X-ray structure of the C-terminal region of KKT4 shows that it has a tandem BRCT (BRCA1 C Terminus) domain fold with a sulfate ion bound in a typical binding site for a phosphorylated serine or threonine. Here we present the <sup>1</sup>H, <sup>13</sup>C and <sup>15</sup>N resonance assignments for the BRCT domain of KKT4 (KKT4<sup>463–645</sup>) from <i>T. brucei</i>. We show that the BRCT domain can bind phosphate ions in solution using residues involved in sulfate ion binding in the X-ray structure. We have used these assignments to characterise the secondary structure and backbone dynamics of the BRCT domain in solution. Mutating the residues involved in phosphate ion binding in <i>T. brucei</i> KKT4 BRCT results in growth defects confirming the importance of the BRCT phosphopeptide-binding activity in vivo. These results may facilitate rational drug design efforts in the future to combat diseases caused by kinetoplastid parasites.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"15 - 25"},"PeriodicalIF":0.8,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that plays a key role in the development and function of the liver, pancreas, and kidney. HNF1β plays a key role in early vertebrate development and the morphogenesis of these organs. In humans, heterozygous mutations in the HNF1B gene can result in organ dysplasia, making it the most common cause of developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. Pathogenic variants in the HNF1B gene are known to cause various diseases, including maturity-onset diabetes of the young and developmental renal diseases. This study presents the backbone resonance assignments of HNF1β POUS and POUHD domains, which are highly conserved domains required for the recognition of double-stranded DNA. Our data will be useful for NMR studies to verify the altered structures and functions of mutant HNF1B proteins that can induce developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. This study will provide the structural basis for future studies to elucidate the molecular mechanisms underlying how mutations in HNF1β cause diseases.
肝细胞核因子 1β(HNF1β)是一种转录因子,在肝脏、胰腺和肾脏的发育和功能中起着关键作用。HNF1β 在脊椎动物的早期发育和这些器官的形态发生中起着关键作用。在人类中,HNF1B 基因的杂合子突变可导致器官发育不良,是导致肾脏发育疾病(包括肾囊肿、肾畸形和家族性肾小球发育不全囊性肾病)的最常见原因。已知 HNF1B 基因的致病变异可导致多种疾病,包括成熟期发病的青年糖尿病和发育性肾病。本研究展示了 HNF1β POUS 和 POUHD 结构域的骨架共振分配,这两个结构域是识别双链 DNA 所需的高度保守结构域。我们的数据将有助于核磁共振研究验证突变型 HNF1B 蛋白结构和功能的改变,这些突变型 HNF1B 蛋白可诱发肾脏发育疾病,包括肾囊肿、肾畸形和家族性肾小球发育不全囊性肾病。这项研究将为今后的研究提供结构基础,以阐明 HNF1β 突变如何导致疾病的分子机制。
{"title":"1H, 13C and 15N backbone resonance assignments of hepatocyte nuclear factor-1-beta (HNF1β) POUS and POUHD","authors":"Sayaka Hokazono, Eri Imagawa, Daishi Hirano, Takahisa Ikegami, Kimihiko Oishi, Tsuyoshi Konuma","doi":"10.1007/s12104-024-10168-4","DOIUrl":"10.1007/s12104-024-10168-4","url":null,"abstract":"<div><p>Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that plays a key role in the development and function of the liver, pancreas, and kidney. HNF1β plays a key role in early vertebrate development and the morphogenesis of these organs. In humans, heterozygous mutations in the <i>HNF1B</i> gene can result in organ dysplasia, making it the most common cause of developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. Pathogenic variants in the <i>HNF1B</i> gene are known to cause various diseases, including maturity-onset diabetes of the young and developmental renal diseases. This study presents the backbone resonance assignments of HNF1β POU<sub>S</sub> and POU<sub>HD</sub> domains, which are highly conserved domains required for the recognition of double-stranded DNA. Our data will be useful for NMR studies to verify the altered structures and functions of mutant <i>HNF1B</i> proteins that can induce developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. This study will provide the structural basis for future studies to elucidate the molecular mechanisms underlying how mutations in HNF1β cause diseases.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"59 - 63"},"PeriodicalIF":0.8,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mediator complex is a key component that bridges various transcription activators and RNA polymerase during eukaryotic transcription initiation. The Arabidopsis thaliana Med25 (aMed25), a subunit of the Mediator complex, plays important roles in regulating hormone signaling, biotic and abiotic stress responses and plant development by interacting with a variety of transcription factors through its activator-interacting domain (ACID). However, the recognition mechanism of aMed25-ACID for various transcription factors remains unknown. Here, we report the nearly complete 1H, 13C, and 15N backbone and side chain resonance assignments of aMED25-ACID (residues 551–681). TALOS-N analysis revealed that aMED25-ACID structure is comprised of three α-helices and seven β-strands, which lacks the C-terminal α-helix existing in the human MED25-ACID. This study lays a foundation for further research on the structure-function relationship of aMED25-ACID.
{"title":"Chemical shift assignments of the ACID domain of MED25, a subunit of the mediator complex in Arabidopsis thaliana","authors":"Yue Xiong, Jiang Zhu, Rui Hu, Ying Li, Yunhuang Yang, Maili Liu","doi":"10.1007/s12104-024-10164-8","DOIUrl":"10.1007/s12104-024-10164-8","url":null,"abstract":"<div><p>Mediator complex is a key component that bridges various transcription activators and RNA polymerase during eukaryotic transcription initiation. The <i>Arabidopsis thaliana</i> Med25 (aMed25), a subunit of the Mediator complex, plays important roles in regulating hormone signaling, biotic and abiotic stress responses and plant development by interacting with a variety of transcription factors through its activator-interacting domain (ACID). However, the recognition mechanism of aMed25-ACID for various transcription factors remains unknown. Here, we report the nearly complete <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N backbone and side chain resonance assignments of aMED25-ACID (residues 551–681). TALOS-N analysis revealed that aMED25-ACID structure is comprised of three α-helices and seven β-strands, which lacks the C-terminal α-helix existing in the human MED25-ACID. This study lays a foundation for further research on the structure-function relationship of aMED25-ACID.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"27 - 31"},"PeriodicalIF":0.8,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-10DOI: 10.1007/s12104-023-10162-2
Chunhua Yuan, Alexandar L. Hansen, Lei Bruschweiler-Li, Rafael Brüschweiler
Human K-Ras protein, which is a member of the GTPase Ras family, hydrolyzes GTP to GDP and concomitantly converts from its active to its inactive state. It is a key oncoprotein, because several mutations, particularly those at residue position 12, occur with a high frequency in a wide range of human cancers. The K-Ras protein is therefore an important target for developing therapeutic anti-cancer agents. In this work we report the almost complete sequence-specific resonance assignments of wild-type and the oncogenic G12C and G12D mutants in the GTP-complexed active forms, including the functionally important Switch I and Switch II regions. These assignments serve as the basis for a comprehensive functional dynamics study of wild-type K-Ras and its G12 mutants.
{"title":"NMR 1H, 13C, 15N backbone resonance assignments of wild-type human K-Ras and its oncogenic mutants G12D and G12C bound to GTP","authors":"Chunhua Yuan, Alexandar L. Hansen, Lei Bruschweiler-Li, Rafael Brüschweiler","doi":"10.1007/s12104-023-10162-2","DOIUrl":"10.1007/s12104-023-10162-2","url":null,"abstract":"<div><p>Human K-Ras protein, which is a member of the GTPase Ras family, hydrolyzes GTP to GDP and concomitantly converts from its active to its inactive state. It is a key oncoprotein, because several mutations, particularly those at residue position 12, occur with a high frequency in a wide range of human cancers. The K-Ras protein is therefore an important target for developing therapeutic anti-cancer agents. In this work we report the almost complete sequence-specific resonance assignments of wild-type and the oncogenic G12C and G12D mutants in the GTP-complexed active forms, including the functionally important Switch I and Switch II regions. These assignments serve as the basis for a comprehensive functional dynamics study of wild-type K-Ras and its G12 mutants.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"7 - 13"},"PeriodicalIF":0.8,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72012975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-03DOI: 10.1007/s12104-023-10156-0
Alexander M. Barclay, Dhruva D. Dhavale, Collin G. Borcik, Moses H. Milchberg, Paul T. Kotzbauer, Chad M. Rienstra
Fibrils of the protein α-synuclein (Asyn) are implicated in the pathogenesis of Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy. Numerous forms of Asyn fibrils have been studied by solid-state NMR and resonance assignments have been reported. Here, we report a new set of 13C, 15N assignments that are unique to fibrils obtained by amplification from postmortem brain tissue of a patient diagnosed with Lewy Body Dementia.
{"title":"13C and 15N resonance assignments of alpha synuclein fibrils amplified from Lewy Body Dementia tissue","authors":"Alexander M. Barclay, Dhruva D. Dhavale, Collin G. Borcik, Moses H. Milchberg, Paul T. Kotzbauer, Chad M. Rienstra","doi":"10.1007/s12104-023-10156-0","DOIUrl":"10.1007/s12104-023-10156-0","url":null,"abstract":"<div><p>Fibrils of the protein α-synuclein (Asyn) are implicated in the pathogenesis of Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy. Numerous forms of Asyn fibrils have been studied by solid-state NMR and resonance assignments have been reported. Here, we report a new set of <sup>13</sup>C, <sup>15</sup>N assignments that are unique to fibrils obtained by amplification from postmortem brain tissue of a patient diagnosed with Lewy Body Dementia.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"17 2","pages":"281 - 286"},"PeriodicalIF":0.9,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71908574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-02DOI: 10.1007/s12104-023-10161-3
Helena Tossavainen, Ilona Pitkänen, Lina Antenucci, Chandan Thapa, Perttu Permi
S. aureus resistance to antibiotics has increased rapidly. MRSA strains can simultaneously be resistant to many different classes of antibiotics, including the so-called “last-resort” drugs. Resistance complicates treatment, increases mortality and substantially increases the cost of treatment. The need for new drugs against (multi)resistant S. aureus is high. M23B family peptidoglycan hydrolases, enzymes that can kill S. aureus by cleaving glycine-glycine peptide bonds in S. aureus cell wall are attractive targets for drug development because of their binding specificity and lytic activity. M23B enzymes lysostaphin, LytU and LytM have closely similar catalytic domain structures. They however differ in their lytic activities, which can arise from non-conserved residues in the catalytic groove and surrounding loops or differences in dynamics. We report here the near complete 1H/13C/15N resonance assignment of the catalytic domain of LytM, residues 185–316. The chemical shift data allow comparative structural and functional studies between the enzymes and is essential for understanding how these hydrolases degrade the cell wall.
{"title":"Chemical shift assignments of the catalytic domain of Staphylococcus aureus LytM","authors":"Helena Tossavainen, Ilona Pitkänen, Lina Antenucci, Chandan Thapa, Perttu Permi","doi":"10.1007/s12104-023-10161-3","DOIUrl":"10.1007/s12104-023-10161-3","url":null,"abstract":"<div><p><i>S. aureus</i> resistance to antibiotics has increased rapidly. MRSA strains can simultaneously be resistant to many different classes of antibiotics, including the so-called “last-resort” drugs. Resistance complicates treatment, increases mortality and substantially increases the cost of treatment. The need for new drugs against (multi)resistant <i>S. aureus</i> is high. M23B family peptidoglycan hydrolases, enzymes that can kill <i>S. aureus</i> by cleaving glycine-glycine peptide bonds in <i>S. aureus</i> cell wall are attractive targets for drug development because of their binding specificity and lytic activity. M23B enzymes lysostaphin, LytU and LytM have closely similar catalytic domain structures. They however differ in their lytic activities, which can arise from non-conserved residues in the catalytic groove and surrounding loops or differences in dynamics. We report here the near complete <sup>1</sup>H/<sup>13</sup>C/<sup>15</sup>N resonance assignment of the catalytic domain of LytM, residues 185–316. The chemical shift data allow comparative structural and functional studies between the enzymes and is essential for understanding how these hydrolases degrade the cell wall.</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":"18 1","pages":"1 - 5"},"PeriodicalIF":0.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}