6izc

Crystal structure of the chromosome-encoded beta-lactamase of Vibrio parahaemolyticus

spinqualitylabelsall models 6izc, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6izc is a 2 chain structure with sequence from Vibrio parahaemolyticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: 1PE, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A3E1IK87_VIBPH Publication Abstract from PubMed beta-Lactams are the most widely used antibiotics in treating bacterial infections. However, they are rarely applied in infections caused by Vibrio parahaemolyticus, as the bacterium is intrinsically resistant to penicillins by expressing beta-lactamase. Here we report structural characterization of the CARB beta-lactamase from V. parahaemolyticus (CARB-20). CARB-20 is a class A beta-lactamase, belonging to subclass A1 (containing 70STFKAL75, 130SDNTAANL137, 164RXEXXLN170, 231VGDKTG236, etc.), group LSBL2 (with the disulfide bridge C77-C123, motif 231IADRSGAG238 and R244). CARB-20 adopts a typical subclass A1 beta-lactamase fold consisting of two domains. Its active site is constituted by four conserved motifs, similar to that of known subclass A1 beta-lactamases. Analysis of the active site structure reveals its substrate preference for penicillin, ampicillin and carbenicillin but not for latterly developed cephalosporins. Meanwhile, beta-lactamase inhibitors such as clavulanate and sulbactam can well fit into the active site, supporting beta-lactams combined with beta-lactamase inhibitors as a potential approach for treating infection of V. parahaemolyticus. The residues around the active site show certain variations, which can be useful for specific inhibitor design. In the directed evolution experiment, CARB-20 exhibited plasticity in developing significant resistance to inhibitors by accumulated residue substitutions. Therefore, careful monitoring of enzyme mutations is necessary for successfully applying beta-lactam/beta-lactamase inhibitor combination therapy. Taken together, our results open up an avenue of inhibitor design targeting vibrio beta-lactamases, facilitating the application of beta-lactams in treating vibrio infections. Structural analysis of the CARB beta-lactamase from Vibrio parahaemolyticus facilitates application of the beta-lactam/beta-lactamase inhibitor therapy.,Li P, Liu C, Li B, Ma Q Biochimie. 2020 Apr - May;171-172:213-222. doi: 10.1016/j.biochi.2020.03.011., Epub 2020 Mar 13. PMID:32179166 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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