5hfo

CRYSTAL STRUCTURE OF OXA-232 BETA-LACTAMASE

spinqualitylabelsall models 5hfo, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hfo is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.21Å Ligands: CL, GOL, KCX, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function M4JTK1_ECOLX Publication Abstract from PubMed Increasing numbers of variants of the carbapenem-hydrolyzing class D beta-lactamase OXA-48 are identified in Enterobacterales worldwide. Among them, OXA-181 and OXA-232 are of particular interest, as they differ from each other by a single amino acid substitution at position 214 (R in OXA-181 and S in OXA-232) that results in reduced carbapenem-hydrolyzing activity for OXA-232. To investigate the role of amino acid position 214 (AA214), the X-ray structure of OXA-232 was determined and AA214 of OXA-48 and of OXA-232 was replaced by G, L, D, E, S, R, and K using site-directed mutagenesis. These mutants were phenotypically characterized, and three mutants of OXA-232 were purified to study their steady-state kinetic properties. The X-ray structure of OXA-232 along with molecular modeling studies showed that the interaction via a salt bridge between R214 and D159 in OXA-48 is not possible with the G214 or S214 mutation. In contrast, with K214, which is also positively charged, the interaction with D159 is maintained. With the E214 mutant, an alternative binding conformation of imipenem that is not compatible with a nucleophilic attack by S70 was evidenced. Thus, imipenem has a very poor apparent affinity for the E214 mutant because of its nonproductive binding mode. Similarly, we could explain the lack of temocillin hydrolysis by the OXA-232-S214E mutant, which is due to the unfavorable interaction between the negatively charged R1 substituent of temocillin with the E214 residue. Overall, we demonstrate that AA214 in OXA-48-like beta-lactamases is critical for the carbapenemase activity. Role of Arginine 214 in the Substrate Specificity of OXA-48.,Oueslati S, Retailleau P, Marchini L, Berthault C, Dortet L, Bonnin RA, Iorga BI, Naas T Antimicrob Agents Chemother. 2020 Apr 21;64(5). pii: AAC.02329-19. doi:, 10.1128/AAC.02329-19. Print 2020 Apr 21. PMID:32071047 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA