View source for 8gcs


==XFEL structure of Mycobacterium tuberculosis beta lactamase microcrystals mixed with sulbactam for 3 ms==
<StructureSection load='8gcs' size='340' side='right'caption='[[8gcs]], [[Resolution|resolution]] 2.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gcs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_str._Beijing/W_BT1 Mycobacterium tuberculosis str. Beijing/W BT1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GCS 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]] 2.62&#8491;</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=8gcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gcs OCA], [https://pdbe.org/8gcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gcs RCSB], [https://www.ebi.ac.uk/pdbsum/8gcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gcs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLAC_MYCBO BLAC_MYCBO] Extended spectrum beta-lactamase (ESBL) that inactivates beta-lactam antibiotics by hydrolyzing the amide group of the beta-lactam ring. Displays high levels of penicillinase and cephalosporinase activity as well as measurable activity with carbapenems, including imipenem and meropenem. Plays a primary role in the intrinsic resistance of mycobacteria to beta-lactam antibiotics.[UniProtKB:P9WKD3]
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis str. Beijing/W BT1]]
[[Category: Malla TN]]
[[Category: Schmidt M]]