8gcv: Difference between revisions
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==XFEL structure of Mycobacterium tuberculosis beta lactamase microcrystals== | |||
<StructureSection load='8gcv' size='340' side='right'caption='[[8gcv]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8gcv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GCV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gcv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gcv OCA], [https://pdbe.org/8gcv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gcv RCSB], [https://www.ebi.ac.uk/pdbsum/8gcv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gcv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A655AHQ9_MYCTX A0A655AHQ9_MYCTX] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
For decades, researchers have elucidated essential enzymatic functions on the atomic length scale by tracing atomic positions in real-time. Our work builds on possibilities unleashed by mix-and-inject serial crystallography (MISC) at X-ray free electron laser facilities. In this approach, enzymatic reactions are triggered by mixing substrate or ligand solutions with enzyme microcrystals. Here, we report in atomic detail (between 2.2 and 2.7 A resolution) by room-temperature, time-resolved crystallography with millisecond time-resolution (with timepoints between 3 ms and 700 ms) how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam (SUB). Our results reveal ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection all from the same set of MISC data, detailing how SUB approaches the catalytic clefts and binds to the enzyme noncovalently before reacting to a trans-enamine. This was made possible in part by the application of singular value decomposition to the MISC data using a program that remains functional even if unit cell parameters change up to 3 A during the reaction. | |||
Heterogeneity in M. tuberculosis beta-lactamase inhibition by Sulbactam.,Malla TN, Zielinski K, Aldama L, Bajt S, Feliz D, Hayes B, Hunter M, Kupitz C, Lisova S, Knoska J, Martin-Garcia JM, Mariani V, Pandey S, Poudyal I, Sierra RG, Tolstikova A, Yefanov O, Yoon CH, Ourmazd A, Fromme P, Schwander P, Barty A, Chapman HN, Stojkovic EA, Batyuk A, Boutet S, Phillips GN Jr, Pollack L, Schmidt M Nat Commun. 2023 Sep 7;14(1):5507. doi: 10.1038/s41467-023-41246-1. PMID:37679343<ref>PMID:37679343</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8gcv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis]] | |||
[[Category: Malla TN]] | |||
[[Category: Schmidt M]] | |||
Latest revision as of 17:42, 20 September 2023
XFEL structure of Mycobacterium tuberculosis beta lactamase microcrystalsXFEL structure of Mycobacterium tuberculosis beta lactamase microcrystals
Structural highlights
FunctionPublication Abstract from PubMedFor decades, researchers have elucidated essential enzymatic functions on the atomic length scale by tracing atomic positions in real-time. Our work builds on possibilities unleashed by mix-and-inject serial crystallography (MISC) at X-ray free electron laser facilities. In this approach, enzymatic reactions are triggered by mixing substrate or ligand solutions with enzyme microcrystals. Here, we report in atomic detail (between 2.2 and 2.7 A resolution) by room-temperature, time-resolved crystallography with millisecond time-resolution (with timepoints between 3 ms and 700 ms) how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam (SUB). Our results reveal ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection all from the same set of MISC data, detailing how SUB approaches the catalytic clefts and binds to the enzyme noncovalently before reacting to a trans-enamine. This was made possible in part by the application of singular value decomposition to the MISC data using a program that remains functional even if unit cell parameters change up to 3 A during the reaction. Heterogeneity in M. tuberculosis beta-lactamase inhibition by Sulbactam.,Malla TN, Zielinski K, Aldama L, Bajt S, Feliz D, Hayes B, Hunter M, Kupitz C, Lisova S, Knoska J, Martin-Garcia JM, Mariani V, Pandey S, Poudyal I, Sierra RG, Tolstikova A, Yefanov O, Yoon CH, Ourmazd A, Fromme P, Schwander P, Barty A, Chapman HN, Stojkovic EA, Batyuk A, Boutet S, Phillips GN Jr, Pollack L, Schmidt M Nat Commun. 2023 Sep 7;14(1):5507. doi: 10.1038/s41467-023-41246-1. PMID:37679343[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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