3qnb | pdb_00003qnb

Crystal Structure of an Engineered OXA-10 Variant with Carbapenemase Activity, OXA-10loop24

spinqualitylabelsall models 3qnb, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qnb is a 4 chain structure with sequence from [alpha Escherichia coli dh5[alpha]]. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, SO4 NonStd Res: KCX Related: 3qnc Gene: blaOXA-10(loop24) (Escherichia coli DH5[alpha]) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Class D beta-lactamases with carbapenemase activity are emerging as carbapenem-resistance determinants in gram-negative bacterial pathogens, mostly Acinetobacter baumannii and Klebsiella pneumoniae. Carbapenemase activity is an unusual feature among class D beta-lactamases, and the structural elements responsible for this activity remain unclear. Based on structural and molecular dynamics data, we previously hypothesized a potential role of the residues located in the short-loop connecting strands beta5 and beta6 (the beta5-beta6 loop) in conferring the carbapenemase activity of the OXA-48 enzyme. In this work, the narrow-spectrum OXA-10 class D beta-lactamase, which is unable to hydrolyze carbapenems, was used as a model to investigate the possibility of evolving carbapenemase activity by replacement of the beta5-beta6 loop with those present in three different lineages of class D carbapenemases (OXA-23, OXA-24, and OXA-48). Biological assays and kinetic measurements showed that all three OXA-10-derived hybrids acquired significant carbapenemase activity. Structural analysis of the OXA-10loop24 and OXA-10loop48 hybrids revealed no significant changes in the molecular fold of the enzyme, except for the orientation of the substituted beta5-beta6 loops, which was reminiscent of that found in their parental enzymes. These results demonstrate the crucial role of the beta5-beta6 loop in the carbapenemase activity of class D beta-lactamases, and provide previously unexplored insights into the mechanism by which these enzymes can evolve carbapenemase activity. Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D beta-lactamase OXA-10 by rational protein design.,De Luca F, Benvenuti M, Carboni F, Pozzi C, Rossolini GM, Mangani S, Docquier JD Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18424-9. Epub 2011 Oct 31. PMID:22042844 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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