8gcs | pdb_00008gcs

XFEL structure of Mycobacterium tuberculosis beta lactamase microcrystals mixed with sulbactam for 3 ms

spinqualitylabelsall models 8gcs, resolution 2.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gcs is a 4 chain structure with sequence from Mycobacterium tuberculosis str. Beijing/W BT1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.62Å Ligands: PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA