Pub Date : 2023-07-07DOI: 10.1107/s2053273323097395
Ling Xu, Kevin Chung, Tianshuo Liu, Pengxin Chai, Junhui Peng, Swapnil Devarkar, A. Pyle
{"title":"Group II intron splicing mechanisms – ribozymes and retrotransposons","authors":"Ling Xu, Kevin Chung, Tianshuo Liu, Pengxin Chai, Junhui Peng, Swapnil Devarkar, A. Pyle","doi":"10.1107/s2053273323097395","DOIUrl":"https://doi.org/10.1107/s2053273323097395","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139362144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323097887
Daniel Olds, Phil Maffettone, Bruce Ravel, Thomas Caswell, Stuart Campbell, H. Joress
{"title":"Realizing autonomous, real-time, AI-driven multimodal studies at X-ray light sources","authors":"Daniel Olds, Phil Maffettone, Bruce Ravel, Thomas Caswell, Stuart Campbell, H. Joress","doi":"10.1107/s2053273323097887","DOIUrl":"https://doi.org/10.1107/s2053273323097887","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139362160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323099801
M. Mcleod, Siddhi Balamurali, Robert Thorne, T. Holyoak
Phosphoenolpyruvate carboxykinases (PEPCK) are metabolic enzymes controlling the TCA - cycle. They have been implicated as potential targets in treating diabetes, cancer, and Mycobacterium tuberculosis infections, and have a role in aging and longevity. These enzymes interconvert oxaloacetic acid (OAA) to form phosphoenolpyruvate (PEP). PEPCKs are widely distributed across life and occur in three classes depending on the nature of phosphoryl donor used for their catalyzed reactions. Of the three classes, the most understudied are PPi-dependent PEPCKs, which are structurally and functionally distinct from the nucleotide -using classes (GTP and ATP). PPi-dependent PEPCKs have a conserved core (~60 kDa) that comprises the general fold of both nucleotide-dependent classes. However, their structure has significant additions (~70 kDa) that form allosteric sites and oligomeric interfaces, and that have likely l ed to divergent functional properties. Here we have used size-exclusion chromatography, enzyme kinetics, crystallography and small-angle x-ray scattering to understand the structural and functional aspects of three PPi - dependent PEPCK isozymes. Actinomyces israelii PPi-dependent PEPCK is found as a constitutive dimer with significantly reduced activity. Propionibacterium freudenreichii (Pf - PPi-PEPCK) differs from its nucleotide counterparts in its enzyme - catalyzed reaction, metal - dependencies, and alloste rically induced activity - regulation via monomer - dimer transition. The third isozyme is from the human parasite Entamoeba histolytica (Eh-PPi-PEPCK). Eh-PPi-PEPCK occurs in three paralogs with different sequences,
磷酸烯醇丙酮酸羧激酶（PEPCK）是控制 TCA 循环的代谢酶。它们被认为是治疗糖尿病、癌症和结核分枝杆菌感染的潜在靶点，并在衰老和长寿中发挥作用。这些酶将草酰乙酸（OAA）转化为磷酸烯醇丙酮酸（PEP）。PEPCKs 广泛分布于生命体中，根据其催化反应中使用的磷酸供体的性质分为三类。在这三类PEPCKs中，研究最不深入的是依赖PPi的PEPCKs，它们在结构上和功能上都有别于使用核苷酸的PEPCKs（GTP和ATP）。依赖 PPi 的 PEPCKs 有一个保守的核心（约 60 kDa），它包含了依赖核苷酸类的一般折叠。然而，它们的结构有明显的附加部分（约 70 kDa），这些附加部分形成了异构位点和低聚物界面，很可能导致了不同的功能特性。在这里，我们利用尺寸排阻色谱法、酶动力学、晶体学和小角 X 射线散射来了解三种 PPi 依赖性 PEPCK 同工酶的结构和功能方面。发现伊斯拉放线菌（Actinomyces israelii）依赖 PPi 的 PEPCK 是一种组成型二聚体，其活性明显降低。弗氏丙酸杆菌（Pf-PPi-PEPCK）在酶催化反应、金属依赖性以及通过单体-二聚体转变的异源诱导活性调节方面与核苷酸同工酶不同。第三个同工酶来自人类寄生虫组织溶解恩塔米巴虫（Eh-PPi-PEPCK）。Eh-PPi-PEPCK 有三个具有不同序列的同工酶、
{"title":"Structural and functional divergence of a 'new' class of phosphoenolpyruvate carboxykinase – insights into allosteric regulation via oligomeric changes","authors":"M. Mcleod, Siddhi Balamurali, Robert Thorne, T. Holyoak","doi":"10.1107/s2053273323099801","DOIUrl":"https://doi.org/10.1107/s2053273323099801","url":null,"abstract":"Phosphoenolpyruvate carboxykinases (PEPCK) are metabolic enzymes controlling the TCA - cycle. They have been implicated as potential targets in treating diabetes, cancer, and Mycobacterium tuberculosis infections, and have a role in aging and longevity. These enzymes interconvert oxaloacetic acid (OAA) to form phosphoenolpyruvate (PEP). PEPCKs are widely distributed across life and occur in three classes depending on the nature of phosphoryl donor used for their catalyzed reactions. Of the three classes, the most understudied are PPi-dependent PEPCKs, which are structurally and functionally distinct from the nucleotide -using classes (GTP and ATP). PPi-dependent PEPCKs have a conserved core (~60 kDa) that comprises the general fold of both nucleotide-dependent classes. However, their structure has significant additions (~70 kDa) that form allosteric sites and oligomeric interfaces, and that have likely l ed to divergent functional properties. Here we have used size-exclusion chromatography, enzyme kinetics, crystallography and small-angle x-ray scattering to understand the structural and functional aspects of three PPi - dependent PEPCK isozymes. Actinomyces israelii PPi-dependent PEPCK is found as a constitutive dimer with significantly reduced activity. Propionibacterium freudenreichii (Pf - PPi-PEPCK) differs from its nucleotide counterparts in its enzyme - catalyzed reaction, metal - dependencies, and alloste rically induced activity - regulation via monomer - dimer transition. The third isozyme is from the human parasite Entamoeba histolytica (Eh-PPi-PEPCK). Eh-PPi-PEPCK occurs in three paralogs with different sequences,","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"26 11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323097760
Jue Liu, Zhijia Du, Michelle Everrett
Neutron scattering has unique advantages for battery research. Neutron scattering is very sensitive to light elements (e.g., H, Li, C, and O), which are the most important ingredients for rechargeable Li/Na - ion batteries. It can also distinguish adjacent transition metal (TM) cations (e.g., Mn, Fe, and Ni) in battery cathodes, especially when conducting isotope substitution experiments. This capability allows accurate investigation of how cation arrangements affect the electrochemistry performance of variou s rechargeable battery cathodes. Neutron scattering can also be used to probe dynamics, particularly ligand anion vibration/lattice dynamic and ionic diffusions, in both electrode and electrolyte materials.
{"title":"Recent development of operando neutron diffraction and its application in studying energy storage materials","authors":"Jue Liu, Zhijia Du, Michelle Everrett","doi":"10.1107/s2053273323097760","DOIUrl":"https://doi.org/10.1107/s2053273323097760","url":null,"abstract":"Neutron scattering has unique advantages for battery research. Neutron scattering is very sensitive to light elements (e.g., H, Li, C, and O), which are the most important ingredients for rechargeable Li/Na - ion batteries. It can also distinguish adjacent transition metal (TM) cations (e.g., Mn, Fe, and Ni) in battery cathodes, especially when conducting isotope substitution experiments. This capability allows accurate investigation of how cation arrangements affect the electrochemistry performance of variou s rechargeable battery cathodes. Neutron scattering can also be used to probe dynamics, particularly ligand anion vibration/lattice dynamic and ionic diffusions, in both electrode and electrolyte materials.","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323099989
Xu Liu
{"title":"Disruption of a key hydrogen-bond network dissociates glucocorticoid receptor-mediated drug efficacy from side effects for anti-inflammation treatment","authors":"Xu Liu","doi":"10.1107/s2053273323099989","DOIUrl":"https://doi.org/10.1107/s2053273323099989","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323097413
Byung-Kuk Yoo, Ryan Miller, Sarah Bowman, Douglas Rees, Kim Lewis
Discovery of antibiotics against Gram - negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which assists in folding and insertion of proteins into the outer membrane, is an attractive target because of its surface location, exposed to the extracellular environment. In this study, we identify dynobactin A, a novel peptide antibiotic from Photorhabdus australis which targets BamA, and unveil two unique unlinked rings by cryogenic electron micros copy. a The novel compound is the fi rst natural product antibiotic of unknown structure solved de novo by this approach (PDB 7T3H). It is a decapeptide of sequence W1 N 2 S3N4 V5H6 S7Y 8 R 9F10, which has two closed rings: 1) a carbon-carbon bond formed between the Trp1 C 6 and the β -carbon of Asn 4 (green box) and 2) an unusual nitrogen-carbon linkage between the His6 imidazole Nε2 and the β - carbon of Tyr8 (orange box). These connections create unfused 4-and 3-constituent rings respectively, resulting in a fl exible peptide, contrasting the fused rings of darobactins. Dynobactin A is one example of natural -product antibiotics acting against the outer membrane protein of Gram - negative bacteria. This study demonstrates how electron microscope accelerates antibiotic discovery by providing unambiguous structures from submicron-sized crystals.
由于革兰氏阴性菌的渗透屏障有限，因此发现针对革兰氏阴性菌的抗生素具有独特的挑战性。BamA 协助蛋白质折叠并插入外膜，由于其表面位置暴露于细胞外环境，因此是一个极具吸引力的靶标。在这项研究中，我们从澳洲光杆菌（Photorhabdus australis）中鉴定出了一种针对 BamA 的新型多肽抗生素--达能菌素 A，并通过低温电子显微复制揭示了两个独特的非连接环。它是序列为 W1 N 2 S3N4 V5H6 S7Y 8 R 9F10 的十肽，有两个闭环：1）Trp1 C 6 与 Asn 4 β - 碳之间形成的碳-碳键（绿色方框）；2）His6 咪唑 Nε2 与 Tyr8 β - 碳之间不同寻常的氮-碳连接（橙色方框）。这些连接分别形成了未融合的 4-和 3-成分环，从而形成了一个易折的肽，与达罗巴肽的融合环形成鲜明对比。达罗菌素 A 是一种天然产物抗生素，可对抗革兰氏阴性细菌的外膜蛋白。这项研究展示了电子显微镜如何通过亚微米级晶体提供明确的结构来加速抗生素的发现。
{"title":"Novel macrocyclic antibiotic structure targeting BamA against gram-negative pathogens","authors":"Byung-Kuk Yoo, Ryan Miller, Sarah Bowman, Douglas Rees, Kim Lewis","doi":"10.1107/s2053273323097413","DOIUrl":"https://doi.org/10.1107/s2053273323097413","url":null,"abstract":"Discovery of antibiotics against Gram - negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which assists in folding and insertion of proteins into the outer membrane, is an attractive target because of its surface location, exposed to the extracellular environment. In this study, we identify dynobactin A, a novel peptide antibiotic from Photorhabdus australis which targets BamA, and unveil two unique unlinked rings by cryogenic electron micros copy. a The novel compound is the fi rst natural product antibiotic of unknown structure solved de novo by this approach (PDB 7T3H). It is a decapeptide of sequence W1 N 2 S3N4 V5H6 S7Y 8 R 9F10, which has two closed rings: 1) a carbon-carbon bond formed between the Trp1 C 6 and the β -carbon of Asn 4 (green box) and 2) an unusual nitrogen-carbon linkage between the His6 imidazole Nε2 and the β - carbon of Tyr8 (orange box). These connections create unfused 4-and 3-constituent rings respectively, resulting in a fl exible peptide, contrasting the fused rings of darobactins. Dynobactin A is one example of natural -product antibiotics acting against the outer membrane protein of Gram - negative bacteria. This study demonstrates how electron microscope accelerates antibiotic discovery by providing unambiguous structures from submicron-sized crystals.","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323098212
S. Meisburger, N. Ando
Diffuse scattering can provide insight into protein dynamics from macromolecular crystallography (MX) experiments. In conventional MX, the protein’s average structure is determined by analyzing Bragg peak intensities. Diffuse scattering signals present in the same diffraction images contain a wealth of information about deviations from the average structure, including lattice disorder and protein breathing motions. We have shown that when diffraction data are measured carefully at room temperature, the diffuse scattering can be processed to obtain a three-dimensional reciprocal space map that is further analyzed to determine correlated motion. To make diffuse scattering techniques more widely available, we have created a python package mdx2 that is both convenient to use and simple to extend and modify. It is lightweight, relying on the scientific python ecosystem for numerical methods, dials and dxtbx for initial processing and data import, and NeXus format for data storage. Mdx2 can be run on the command line or imported as a package, for instance to encapsulate a complete workflow in a Jupyter notebook for reproducible computing and edu cation. Finally, I will discuss our recent efforts to improve performance and scalability toward real-time data reduction at synchrotron beamlines.
{"title":"Reciprocal-space mapping for macromolecular crystallography","authors":"S. Meisburger, N. Ando","doi":"10.1107/s2053273323098212","DOIUrl":"https://doi.org/10.1107/s2053273323098212","url":null,"abstract":"Diffuse scattering can provide insight into protein dynamics from macromolecular crystallography (MX) experiments. In conventional MX, the protein’s average structure is determined by analyzing Bragg peak intensities. Diffuse scattering signals present in the same diffraction images contain a wealth of information about deviations from the average structure, including lattice disorder and protein breathing motions. We have shown that when diffraction data are measured carefully at room temperature, the diffuse scattering can be processed to obtain a three-dimensional reciprocal space map that is further analyzed to determine correlated motion. To make diffuse scattering techniques more widely available, we have created a python package mdx2 that is both convenient to use and simple to extend and modify. It is lightweight, relying on the scientific python ecosystem for numerical methods, dials and dxtbx for initial processing and data import, and NeXus format for data storage. Mdx2 can be run on the command line or imported as a package, for instance to encapsulate a complete workflow in a Jupyter notebook for reproducible computing and edu cation. Finally, I will discuss our recent efforts to improve performance and scalability toward real-time data reduction at synchrotron beamlines.","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323097103
Peter W. R. Corfield, A. M. F. Varona, Tristan B. DaCunha, Nurul B. Eisha, Ahmed Elsayed
{"title":"Further studies on copper cyanide networks","authors":"Peter W. R. Corfield, A. M. F. Varona, Tristan B. DaCunha, Nurul B. Eisha, Ahmed Elsayed","doi":"10.1107/s2053273323097103","DOIUrl":"https://doi.org/10.1107/s2053273323097103","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323097462
Zhihai Liu, Jinhong Wang, Hua Wang, Lin Mei
{"title":"Integrated M and RELION pipeline in a Linux environment","authors":"Zhihai Liu, Jinhong Wang, Hua Wang, Lin Mei","doi":"10.1107/s2053273323097462","DOIUrl":"https://doi.org/10.1107/s2053273323097462","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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