Acta Crystallographica Section A Foundations and Advances最新文献

{"title":"Challenges and successes in determining the structure of arginyltransferase 1 (ATE1)","authors":"Aaron T. Smith","doi":"10.1107/s2053273323097917","DOIUrl":"https://doi.org/10.1107/s2053273323097917","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361457","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}

{"title":"A snowball effect of opening doors and offering sustained support for early career scientists","authors":"Lindsey R. F. Backman","doi":"10.1107/s2053273323097243","DOIUrl":"https://doi.org/10.1107/s2053273323097243","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361631","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}

{"title":"Structural characterization of a small-molecule RNA triple helix complex","authors":"Madeline M. Glennon, Krishna M. Shivakumar, Martina Zafferani, Anita Donlic, Amanda E. Hargrove, Jessica A. Brown","doi":"10.1107/s2053273323096237","DOIUrl":"https://doi.org/10.1107/s2053273323096237","url":null,"abstract":"Three - dimensional (3D) structures of drug targets have been essential in drug design and discovery. Cryogenic -electron microscopy (cryo-EM) is a revolutionary method that has been successful for elucidating the 3D structures of macromolecules, including small RNAs. However, only a handful of RNA - only 3D structures have been solved and none are in complex with a drug-like small molecule. Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a nuclear -retained long non-coding RNA (lncRNA) with a 3′ - terminal triple helix. The triple helix contributes to the overall stability of MALAT1 by preventing 3′ degradation, resulting in the nuclear accumulation of MALAT1. This over accumulation contributes to the onset and progression of disease, making the triple helix an alluring drug target. Small molecule therapeutics are rapidly expanding due to their deliverability, uptake, and tunability. Promising small molecule libraries comprised of the diphenylfuran (DPF) and diminazene (DMZ) scaffolds, which are known triplex-binding molecules, were developed and initially characterized for their bind ing effects on the MALAT1 triple helix by the Hargrove laboratory. Currently, there is no 3D structure of the MALAT1 triple helix in complex with a small molecule. Herein, I am working towards solving a 3D structure of the MALAT1 triple helix in complex wit h DPF/DMZ small molecules. Thus far, I have grafted the MALAT1 triple helix onto previously solved cryo - EM RNA structures to improve single particle contrast and particle picking. The apo MALAT1 triple helix has been solved at a 5.2 Å resolution; this apo structure will be a reference for density and conformational changes that occur in the presence of a small molecule. I am currently working toward a higher -resolution structure while also optimizing grid conditions for the RNA-small molecule complex. Overall, this study will provide a platform for researchers to better understand how small molecules interact with the MALAT1","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361636","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}

{"title":"The structure of the translating bacterial ribosome at 1.55 Å resolution","authors":"Simon Fromm, Kate M. O’Connor, Michael Purdy, P. R. Bhatt, Gary Longharn, John F. Atkins, Ahmad Jomaa, Simone Mattei","doi":"10.1107/s2053273323098674","DOIUrl":"https://doi.org/10.1107/s2053273323098674","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361644","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}

{"title":"A perfect liaison: combining MicroED with PXRD","authors":"J. Merkelbach, Christian Jandl, Danny Stam, Sebastian Schegk","doi":"10.1107/s2053273323099175","DOIUrl":"https://doi.org/10.1107/s2053273323099175","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361725","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}

{"title":"Improving access and throughput of the MX beamlines at Diamond Light Source, UK","authors":"M. Mazzorana, David Aragao, Neil Paterson, Elliot Nelson, Felicity Bertram, Dave Hall","doi":"10.1107/s2053273323097607","DOIUrl":"https://doi.org/10.1107/s2053273323097607","url":null,"abstract":"The MX group at Diamond Light Source offers a suite of seven macromolecular crystallography (MX) beamlines covering a variety of setups and techniques to meet the demands of the user community. This selection of instruments allows access to a wide range of focusing, energy, throughput capabilities as well as numerous approaches including in-situ , serial crystallography, and fragment - based drug discovery.","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361852","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}

{"title":"Understanding how the Pel polysaccharide is modified for use in the Pseudomonas aeruginosa biofilm","authors":"Jaime C. Van Loon, F. Le Mauff, E. Kitova, Stephanie Gilbert, Mario A. Vargas, Erum Razvi, John S. Klassen, Donald C. Sheppard, P. L. Howell","doi":"10.1107/s2053273323098777","DOIUrl":"https://doi.org/10.1107/s2053273323098777","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139362089","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}

{"title":"Challenges and capabilities of quantum crystallography for locating hydrogen atoms in transition metal hydrides","authors":"M. Woińska, S. Pawlędzio, A. Hoser, M. Chodkiewicz, K. Woźniak","doi":"10.1107/s2053273323099345","DOIUrl":"https://doi.org/10.1107/s2053273323099345","url":null,"abstract":"Transition metal (TM) hydrides are versatile compounds with multiple applications in catalysis, energy conversion, and the search for hydrogen storage materials or superconductors. Therefore, determining the structure of these compounds with X -ray diffraction is essential for many areas of research. However, this is hampered by the challenges of locating the position of hydrogen with X - rays, which are even more aggravated in the case of hydrogen atoms bonded to a TM atom. Furthermore, collecting high - quality, let alone high-resolution X -ray d ata, for TM hydrides, is an arduous task. It is also difficult to collect neutron data that could provide reliable information about hydrogen positions. TM hydride complexes are also computationally demanding, which makes them difficult to analyze using quantu m crystallographic methods. Hirshfeld atom refinement (HAR) is a quantum crystallographic method that has been proven to locate hydrogen atoms bonded to light elements with accuracy and precision very close to that of neutron experiments, based on standard resolution X - ray data [1]. In some cases, HAR has been reported to improve the positions of hydrogen atoms in TM - H bonds considerably [1, 2], as compared to the Independent Atom Model (IAM). The goal of this study was to evaluate the capabilities of HAR in terms of establishing the positions of hydrogen atoms, especially in TM - H bonds, and to investigate the influence of different parameters adjustable in the refinement on the final result. The following factors were considered: including interactions with the crystal environment, taking into account relativistic effects, changing the DFT functional used for wave function calculations (B3LYP, PBE, M06 - 2X), and selecting the basis set. Another aspect considered in the study was the role of treatment of hydrogen thermal","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139362166","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}

{"title":"Structural and biochemical investigation of a novel natural product amination domain","authors":"Michael R. Rankin, D. Khare, Estefanía Martínez Valdivia, David H. Sherman, W. Gerwick, A. Mapp, Janet L. Smith","doi":"10.1107/s2053273323098054","DOIUrl":"https://doi.org/10.1107/s2053273323098054","url":null,"abstract":"","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361511","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}

{"title":"Refinement of crystal structures at ultralow resolution with assistance from AlphaFold modeling and Rosetta optimization","authors":"Wen Wang, Wayne A. Hendrickson","doi":"10.1107/s2053273323099758","DOIUrl":"https://doi.org/10.1107/s2053273323099758","url":null,"abstract":"Crystals of large macromolecular complexes often diffract quite poorly, typically having high solvent content, relatively feeb le lattice contacts, quite weak subunit associations, and somewhat fl exible interdomain linkages. Although resolution may be limited to dmin > 7-8 Å, the diffraction amplitudes should suffice, in principle, to specify conformational torsion angles; however, at such ultralow resolution, realizing and maintaining a suitable model within the radius of refinement convergence is a challenge. Important insights into biological processes may be obtained, but only if structural validity can be assured. Having successfully refined a four - copy structure of Hsp70 DnaK in the S-state at 7.7 Å resolution as rigid bodies (Wang et al. , Mol. Cell 81 , 3919, 2021), we set out to refine a crystal structure of ryanodine receptor RyR1 at 8.0 Å resolution by having multiple quasi - rigid bodies to comprise the 5037 residues in each protomer of the RyR1 -tetramer as complexed with calstabin. After molecular replacement from a 65% -complete cryo-EM model at 3.6 Å resolution (des Georges et al. , Cell 167 , 145, 2016), the structure was refined from a single rigid-body (R free = 0.53), through five linked rigid bodies (R free = 0.47), and fi nally as 18 linked domains (R free = 0.43) identified in the cryo-EM analysis and then sub-divided as dictated by (F o - F c ) difference map and the R free analysis. We then turned to AlphaFold, presuming that the process had stalled due to incompleteness and uncertainty in the initial model. Trials showed that AlphaFold - predicted domains reduced Rfree when fitted into crystal density. We then systematically identified such AlphaFold - modeled domains and obtained substantial improvement (Rfree = 0.38). Further improvement followed after Rosetta refinement using tight restraints in the phenix.rosetta_refine module (R free","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"373 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361600","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}