4Y0O
Crystal structure of OXA-58, a carbapenem hydrolyzing Class D beta-lactamase from Acinetobacter baumanii.
Summary for 4Y0O
| Entry DOI | 10.2210/pdb4y0o/pdb |
| Related | 4Y0T 4Y0U |
| Descriptor | Beta-lactamase (2 entities in total) |
| Functional Keywords | oxa-58, a. baumannii, carbapenemase, beta lactamase, hydrolase |
| Biological source | Acinetobacter baumannii |
| Total number of polymer chains | 1 |
| Total formula weight | 31498.21 |
| Authors | Pratap, S.,Katiki, M.,Gill, P.,Golemi-Kotra, D.,Kumar, P. (deposition date: 2015-02-06, release date: 2016-01-13, Last modification date: 2025-04-09) |
| Primary citation | Pratap, S.,Katiki, M.,Gill, P.,Kumar, P.,Golemi-Kotra, D. Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D beta-Lactamase of Acinetobacter baumannii. Antimicrob.Agents Chemother., 60:75-86, 2015 Cited by PubMed Abstract: Carbapenem-hydrolyzing class D β-lactamases (CHDLs) are a subgroup of class D β-lactamases, which are enzymes that hydrolyze β-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 β-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 6α-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. PubMed: 26459904DOI: 10.1128/AAC.01393-15 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.37 Å) |
Structure validation
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