4x6t

M.tuberculosis betalactamase complexed with inhibitor EC19

spinqualitylabelsall models 4x6t, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4x6t is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: 3Y6, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLAC_MYCTU Publication Abstract from PubMed BlaC, the single chromosomally encoded beta-lactamase of Mycobacterium tuberculosis, has been identified as a promising target for novel therapies that rely upon beta-lactamase inhibition. Boronic acid transition-state inhibitors (BATSIs) are a class of beta-lactamase inhibitors which permit rational inhibitor design by combinations of various R1 and R2 side chains. To explore the structural determinants of effective inhibition, we screened a panel of 25 BATSIs to explore key structure-function relationships. We identified a cefoperazone analogue, EC19, which displayed slow, time-dependent inhibition against BlaC with a potency similar to that of clavulanate (Ki* of 0.65 +/- 0.05 muM). To further characterize the molecular basis of inhibition, we solved the crystallographic structure of the EC19-BlaC(N172A) complex and expanded our analysis to variant enzymes. The results of this structure-function analysis encourage the design of a novel class of beta-lactamase inhibitors, BATSIs, to be used against Mycobacterium tuberculosis. Inhibiting the beta-Lactamase of Mycobacterium tuberculosis (Mtb) with Novel Boronic Acid Transition-State Inhibitors (BATSIs).,Kurz SG, Hazra S, Bethel CR, Romagnoli C, Caselli E, Prati F, Blanchard JS, Bonomo RA ACS Infect Dis. 2015 Jun 12;1(6):234-42. doi: 10.1021/acsinfecdis.5b00003. Epub, 2015 Apr 15. PMID:27622739 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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