4y0o | pdb_00004y0o

Crystal structure of OXA-58, a carbapenem hydrolyzing Class D beta-lactamase from Acinetobacter baumanii.

spinqualitylabelsall models 4y0o, resolution 2.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4y0o is a 1 chain structure with sequence from Acinetobacter baumannii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.37Å Ligands: KCX Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OXA58_ACIBA Class D beta-lactamase which confers resistance to the beta-lactam antibiotics, including penicillins and oxacillin, and moderate resistance to carbapenems such as imipenem; in the DH10B strain of E.coli (PubMed:15616297). Acts via hydrolysis of the beta-lactam ring (PubMed:15616297, PubMed:26459904, PubMed:26701320). Has benzylpenicillin-, oxacillin-, cephalothin- and imipenem-hydrolyzing activities (PubMed:15616297, PubMed:26459904, PubMed:26701320). Publication Abstract from PubMed Carbapenem-hydrolyzing class D beta-lactamases (CHDLs) are a subgroup of class D beta-lactamases, which are enzymes that hydrolyze beta-lactams. They have attracted interest due to the emergence of multidrug-resistant Acinetobacter baumannii, which is not responsive to treatment with carbapenems, the usual antibiotics of choice for this bacterium. Unlike other class D beta-lactamases, these enzymes efficiently hydrolyze carbapenem antibiotics. To explore the structural requirements for the catalysis of carbapenems by these enzymes, we determined the crystal structure of the OXA-58 CHDL of A. baumannii following acylation of its active-site serine by a 6alpha-hydroxymethyl penicillin derivative that is a structural mimetic for a carbapenem. In addition, several point mutation variants of the active site of OXA-58, as identified by the crystal structure analysis, were characterized kinetically. These combined studies confirm the mechanistic relevance of a hydrophobic bridge formed over the active site. This structural feature is suggested to stabilize the hydrolysis-productive acyl-enzyme species formed from the carbapenem substrates of this enzyme. Furthermore, our structural studies provide strong evidence that the hydroxyethyl group of carbapenems samples different orientations in the active sites of CHDLs, and the optimum orientation for catalysis depends on the topology of the active site allowing proper closure of the active site. We propose that CHDLs use the plasticity of the active site to drive the mechanism of carbapenem hydrolysis toward efficiency. Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D beta-Lactamase of Acinetobacter baumannii.,Pratap S, Katiki M, Gill P, Kumar P, Golemi-Kotra D Antimicrob Agents Chemother. 2015 Oct 12;60(1):75-86. doi: 10.1128/AAC.01393-15. PMID:26459904 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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