5l2f

High Resolution Structure of Acinetobacter baumannii beta-lactamase OXA-51 I129L/K83D bound to doripenem

spinqualitylabelsall models 5l2f, resolution 1.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5l2f is a 4 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 1.77Å Ligands: 4J6, ACT, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5QT35_ACIBA Publication Abstract from PubMed OXA-51 is a class D beta-lactamase that is thought to be the native carbapenemase of Acinetobacter baumannii. Many variants of OXA-51 containing active site substitutions have been identified from A. baumannii isolates, and some of these substitutions increase hydrolytic activity toward carbapenem antibiotics. We have determined the high-resolution structures of apo OXA-51 and OXA-51 with one such substitution (I129L) with the carbapenem doripenem trapped in the active site as an acyl-intermediate. The structure shows that acyl-doripenem adopts an orientation very similar to carbapenem ligands observed in the active site of OXA-24/40 (doripenem) and OXA-23 (meropenem). In the OXA-51 variant/doripenem complex, the indole ring of W222 is oriented away from the doripenem binding site, thereby eliminating a clash that is predicted to occur in wildtype OXA-51. Similarly, in the OXA-51 variant complex, L129 adopts a different rotamer compared to I129 in wildtype OXA-51. This alternative position moves its side chain away from the hydroxyethyl moiety of doripenem and relieves another potential clash between the enzyme and carbapenem substrates. Molecular dynamics simulations of OXA-51 and OXA-51 I129L demonstrate that compared to isoleucine, a leucine at this position greatly favors a rotamer that accommodates the ligand. These results provide a molecular justification for how this substitution generates enhanced binding affinity for carbapenems, and therefore helps explain the prevalence of this substitution in clinical OXA-51 variants. The structure of a doripenem-bound OXA-51 class D beta-lactamase variant with enhanced carbapenemase activity.,June CM, Muckenthaler TJ, Schroder EC, Klamer ZL, Wawrzak Z, Powers RA, Szarecka A, Leonard DA Protein Sci. 2016 Sep 16. doi: 10.1002/pro.3040. PMID:27636561 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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