8ec4: Difference between revisions
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==XFEL structure of Mycobacterium tuberculosis beta lactamase microcrystals mixed with sulbactam for 240ms== | |||
<StructureSection load='8ec4' size='340' side='right'caption='[[8ec4]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ec4]] 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=8EC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EC4 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]] 2.35Å</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>, <scene name='pdbligand=TSL:TRANS-ENAMINE+INTERMEDIATE+OF+SULBACTAM'>TSL</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=8ec4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ec4 OCA], [https://pdbe.org/8ec4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ec4 RCSB], [https://www.ebi.ac.uk/pdbsum/8ec4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ec4 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 been determined to elucidate essential enzymatic functions on the atomic lengths scale by tracing atomic positions in real time. Our work builds on new possibilities unleashed by mix-and-inject serial crystallography (MISC) (1-5) at X-ray free electron laser facilities. In this approach, enzymatic reactions are triggered by mixing substrate or ligand solutions with enzyme microcrystals (6) . Here, we report in atomic detail and with millisecond time-resolution how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam (SUB). Our results reveal ligand binding heterogeneity, ligand gating (7-9) , cooperativity, induced fit (10,11) and conformational selection (11-13) all from the same set of MISC data, detailing how SUB approaches the catalytic clefts and binds to the enzyme non-covalently before reacting to a trans- enamine. This was made possible in part by the application of the singular value decomposition (14) to the MISC data using a newly developed program that remains functional even if unit cell parameters change during the reaction. | |||
Heterogeneity in the M. tuberculosis beta-Lactamase Inhibition by Sulbactam.,Schmidt M, Malla TN, Zielinski K, Aldama L, Bajt S, Feliz D, Hayes B, Hunter M, Kupitz C, Lisova S, Knoska J, Martin-Garcia J, Mariani V, Pandey S, Poudyal I, Sierra R, Tolstikova A, Yefanov O, Yoon CH, Ourmazd A, Fromme P, Schwander P, Barty A, Chapman H, Stojkovic E, Batyuk A, Boutet S, Phillips G, Pollack L Res Sq. 2023 Jan 10:rs.3.rs-2334665. doi: 10.21203/rs.3.rs-2334665/v1. Preprint. PMID:36712138<ref>PMID:36712138</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8ec4" 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 21:14, 20 September 2023
XFEL structure of Mycobacterium tuberculosis beta lactamase microcrystals mixed with sulbactam for 240msXFEL structure of Mycobacterium tuberculosis beta lactamase microcrystals mixed with sulbactam for 240ms
Structural highlights
FunctionPublication Abstract from PubMedFor decades, researchers have been determined to elucidate essential enzymatic functions on the atomic lengths scale by tracing atomic positions in real time. Our work builds on new possibilities unleashed by mix-and-inject serial crystallography (MISC) (1-5) at X-ray free electron laser facilities. In this approach, enzymatic reactions are triggered by mixing substrate or ligand solutions with enzyme microcrystals (6) . Here, we report in atomic detail and with millisecond time-resolution how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam (SUB). Our results reveal ligand binding heterogeneity, ligand gating (7-9) , cooperativity, induced fit (10,11) and conformational selection (11-13) all from the same set of MISC data, detailing how SUB approaches the catalytic clefts and binds to the enzyme non-covalently before reacting to a trans- enamine. This was made possible in part by the application of the singular value decomposition (14) to the MISC data using a newly developed program that remains functional even if unit cell parameters change during the reaction. Heterogeneity in the M. tuberculosis beta-Lactamase Inhibition by Sulbactam.,Schmidt M, Malla TN, Zielinski K, Aldama L, Bajt S, Feliz D, Hayes B, Hunter M, Kupitz C, Lisova S, Knoska J, Martin-Garcia J, Mariani V, Pandey S, Poudyal I, Sierra R, Tolstikova A, Yefanov O, Yoon CH, Ourmazd A, Fromme P, Schwander P, Barty A, Chapman H, Stojkovic E, Batyuk A, Boutet S, Phillips G, Pollack L Res Sq. 2023 Jan 10:rs.3.rs-2334665. doi: 10.21203/rs.3.rs-2334665/v1. Preprint. PMID:36712138[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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