Pub Date : 2023-07-07DOI: 10.1107/s2053273323097243
Lindsey R. F. Backman
{"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}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323096237
Madeline M. Glennon, Krishna M. Shivakumar, Martina Zafferani, Anita Donlic, Amanda E. Hargrove, Jessica A. Brown
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
{"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}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323098674
Simon Fromm, Kate M. O’Connor, Michael Purdy, P. R. Bhatt, Gary Longharn, John F. Atkins, Ahmad Jomaa, Simone Mattei
{"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}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323097619
Nick Vukotic, Anton Dmitrienko
{"title":"Innovating together: how strategic academic–industry collaboration can drive advances in materials discovery and create economic and socio-economic benefits","authors":"Nick Vukotic, Anton Dmitrienko","doi":"10.1107/s2053273323097619","DOIUrl":"https://doi.org/10.1107/s2053273323097619","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":"139361665","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/s2053273323097097
Shuchismita Dutta
{"title":"Developing training and educational resources in biomolecular structural biology for diverse audiences","authors":"Shuchismita Dutta","doi":"10.1107/s2053273323097097","DOIUrl":"https://doi.org/10.1107/s2053273323097097","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":"139361681","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/s2053273323099175
J. Merkelbach, Christian Jandl, Danny Stam, Sebastian Schegk
{"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}
Pub Date : 2023-07-07DOI: 10.1107/s2053273323096390
Tiffany L. Kinnibrugh, Tim Fister, Xiaoping Wang, D. Bazak, Ajay Karakoti, Vijayakumar Murugesan
Underutilization of the active material on the positive plate has been a persistent restriction on the performance of lead - acid batteries. Initial utilization of chemically - prepared and PbO2 phases formed in a battery during charge suggests that the stoichiometries change with cycling1 and proximity to oxygen evolution. Moreover, the lifetime of the battery is often limited by the ratio of α and β -Pb O2 and the adhesion between PbO2 and the underlying Pb current collector. This interface, referred to as the “corrosion layer” is thought to contain lead oxides with intermediate composition between PbO and PbO2. Similar phases have previously been identified by mass loss or color change during thermal decomposition of PbO2 to PbO, suggesting at least two phases2, 3. Here, we identify the structure of these phases using multiple in situ analysis techniques. Isolation of PbOx phase/s using TGA enabled determination of a PbOx structure and further analysis with NMR and XPS to provide Pb oxidation states and Pb environments. Finally, we compare these results to data collected from industrial battery plates.
{"title":"Understanding the structure and properties of the elusive non-stoichiometric lead dioxide","authors":"Tiffany L. Kinnibrugh, Tim Fister, Xiaoping Wang, D. Bazak, Ajay Karakoti, Vijayakumar Murugesan","doi":"10.1107/s2053273323096390","DOIUrl":"https://doi.org/10.1107/s2053273323096390","url":null,"abstract":"Underutilization of the active material on the positive plate has been a persistent restriction on the performance of lead - acid batteries. Initial utilization of chemically - prepared and PbO2 phases formed in a battery during charge suggests that the stoichiometries change with cycling1 and proximity to oxygen evolution. Moreover, the lifetime of the battery is often limited by the ratio of α and β -Pb O2 and the adhesion between PbO2 and the underlying Pb current collector. This interface, referred to as the “corrosion layer” is thought to contain lead oxides with intermediate composition between PbO and PbO2. Similar phases have previously been identified by mass loss or color change during thermal decomposition of PbO2 to PbO, suggesting at least two phases2, 3. Here, we identify the structure of these phases using multiple in situ analysis techniques. Isolation of PbOx phase/s using TGA enabled determination of a PbOx structure and further analysis with NMR and XPS to provide Pb oxidation states and Pb environments. Finally, we compare these results to data collected from industrial battery plates.","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":"139361733","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/s2053273323097346
Jonathan R. Herrmann, Natalie Young, A. Kotecha
X - ray diffraction using synchrotron radiation established a routine single-crystal structure determination workflow for small and macromolecules; however, these experiments require large, well -ordered crystals (50 - 100 μm). Growing large protein crystals is a critical bottleneck that is either time-consuming or challenging to overcome, and often smaller crystals are more attainable. Although microfocus beamlines can analyze crystals as small as 10 - 50 μm, they are prone to radiation damage or diffract X - rays weakly, limiting achievable resolution. Electrons are more advantageous than X - rays for the analysis of very small crystals (well below 1 μm in size) because accelerated electrons scatter more readily than X - rays, resulting in a stronger signal from thinner samples. Micro - or nano-crystal elect ron diffraction (MicroED) is thus well - suited for the analysis of small crystals, producing high-resolution 3D structures of small chemical compounds or biological macromolecules. MicroED
利用同步辐射进行 X 射线衍射为小分子和大分子结构测定建立了常规的单晶结构测定工作流程；然而，这些实验需要大而有序的晶体（50 - 100 μm）。生长大型蛋白质晶体是一个关键的瓶颈，要么耗时，要么难以克服，通常较小的晶体更容易实现。虽然微聚焦光束线可以分析小至 10 - 50 微米的晶体，但它们容易受到辐射损伤，或对 X 射线的折射较弱，从而限制了可达到的分辨率。在分析极小晶体（尺寸远小于 1 微米）时，电子比 X 射线更有优势，因为加速电子比 X 射线更容易散射，从而从更薄的样品中获得更强的信号。因此，微米或纳米晶体电子衍射（MicroED）非常适合分析小晶体，生成小化合物或生物大分子的高分辨率三维结构。微电子衍射
{"title":"A complete micro-electron diffraction (MicroED) solution for fast structure determination of macromolecules and small molecules","authors":"Jonathan R. Herrmann, Natalie Young, A. Kotecha","doi":"10.1107/s2053273323097346","DOIUrl":"https://doi.org/10.1107/s2053273323097346","url":null,"abstract":"X - ray diffraction using synchrotron radiation established a routine single-crystal structure determination workflow for small and macromolecules; however, these experiments require large, well -ordered crystals (50 - 100 μm). Growing large protein crystals is a critical bottleneck that is either time-consuming or challenging to overcome, and often smaller crystals are more attainable. Although microfocus beamlines can analyze crystals as small as 10 - 50 μm, they are prone to radiation damage or diffract X - rays weakly, limiting achievable resolution. Electrons are more advantageous than X - rays for the analysis of very small crystals (well below 1 μm in size) because accelerated electrons scatter more readily than X - rays, resulting in a stronger signal from thinner samples. Micro - or nano-crystal elect ron diffraction (MicroED) is thus well - suited for the analysis of small crystals, producing high-resolution 3D structures of small chemical compounds or biological macromolecules. MicroED","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"170 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361735","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/s2053273323098315
Raphael P Hermann, George Yumnan, Michael E Manley, Barry L. Winn, Christina Hoffmann
BaNiO 3-type "hexagonal perovskite" materials are known to exhibit complex phase diagram
众所周知，BaNiO 3 型 "六方包晶 "材料显示出复杂的相图
{"title":"Structure and dynamics in BaTiS3 hexagonal perovskite as seen by neutron scattering","authors":"Raphael P Hermann, George Yumnan, Michael E Manley, Barry L. Winn, Christina Hoffmann","doi":"10.1107/s2053273323098315","DOIUrl":"https://doi.org/10.1107/s2053273323098315","url":null,"abstract":"BaNiO 3-type \"hexagonal perovskite\" materials are known to exhibit complex phase diagram","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361765","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/s2053273323096341
Lina Mardiana, Michael J Hall, Michael R Probert
Cannabidiol (CBD) is a phytocannabinoid which has become increasingly important as an active pharmaceutical ingredient (API), and is commonly isolated and used in its well-known and stable crystalline form (Form 1). However, the crystal structures of a series of CBD analogues, containing a different number of carbon atoms in the alkyl sidechain at C-5’, shows that CBD Form 1 is an outlier in a group demonstrating homologous isomorphism. This indicated the potential existence of an uncharacterised isomorphic CBD polymorph (Form 2). High throughput crystallisation techniques, namely the ENaCt protocol, were used in combination with CBD homologue seeding to search for the presence of this predicted Form 2 of CBD. Optical analysis of the resultant crystals suggested the presence of a new form due to block like crystals rather than the needles associated with Form 1. Single Crystal XRay Diffraction (SCXRD) analysis of these crystals of CBD resulted in a structural model with packing that fits with the isomorphic series. This experiment represents the first example of directed polymorph discovery using high throughput ENaCt techniques.
{"title":"The prediction, observation and analysis of a new form of cannabidiol","authors":"Lina Mardiana, Michael J Hall, Michael R Probert","doi":"10.1107/s2053273323096341","DOIUrl":"https://doi.org/10.1107/s2053273323096341","url":null,"abstract":"Cannabidiol (CBD) is a phytocannabinoid which has become increasingly important as an active pharmaceutical ingredient (API), and is commonly isolated and used in its well-known and stable crystalline form (Form 1). However, the crystal structures of a series of CBD analogues, containing a different number of carbon atoms in the alkyl sidechain at C-5’, shows that CBD Form 1 is an outlier in a group demonstrating homologous isomorphism. This indicated the potential existence of an uncharacterised isomorphic CBD polymorph (Form 2). High throughput crystallisation techniques, namely the ENaCt protocol, were used in combination with CBD homologue seeding to search for the presence of this predicted Form 2 of CBD. Optical analysis of the resultant crystals suggested the presence of a new form due to block like crystals rather than the needles associated with Form 1. Single Crystal XRay Diffraction (SCXRD) analysis of these crystals of CBD resulted in a structural model with packing that fits with the isomorphic series. This experiment represents the first example of directed polymorph discovery using high throughput ENaCt techniques.","PeriodicalId":6903,"journal":{"name":"Acta Crystallographica Section A Foundations and Advances","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139361774","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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