6nz8 | pdb_00006nz8

Structure of carbamylated apo OXA-231 carbapenemase

spinqualitylabelsall models 6nz8, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nz8 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 1.2Å Ligands: CL, KCX, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function H9U2W6_ACIBA Publication Abstract from PubMed The class D beta-lactamase OXA-143 has been described as an efficient penicillinase, oxacillinase, and carbapenemase. The D224A variant, known as OXA-231, was described in 2012 as exhibiting less activity toward imipenem and increased oxacillinase activity. Additionally, the P227S mutation was reported as a case of convergent evolution for homologous enzymes. To investigate the impact of both mutations (D224A and P227S), we describe in this paper a deep investigation of the enzymatic activities of these three homologues. OXA-143(P227S) presented enhanced catalytic activity against ampicillin, oxacillins, aztreonam, and carbapenems. In addition, OXA-143(P227S) was the only member capable of hydrolyzing ceftazidime. These enhanced activities were due to a combination of a higher affinity (lower Km) and a higher turnover number (higher kcat). We also determined the crystal structure of apo OXA-231. As expected, the structure of this variant is very similar to the published OXA-143 structure, except for the two M223 conformations and the absence of electron density for three solvent-exposed loop segments. Molecular dynamics calculations showed that both mutants experience higher flexibility compared to that of the wild-type form. Therefore, our results illustrate that D224A and P227S act as deleterious and positive mutations, respectively, within the evolutionary path of the OXA-143 subfamily toward a more efficient carbapenemase. Importance of the beta5-beta6 Loop for the Structure, Catalytic Efficiency, and Stability of Carbapenem-Hydrolyzing Class D beta-Lactamase Subfamily OXA-143.,Antunes VU, Llontop EE, Vasconcelos FNDC, Lopez de Los Santos Y, Oliveira RJ, Lincopan N, Farah CS, Doucet N, Mittermaier A, Favaro DC Biochemistry. 2019 Aug 27;58(34):3604-3616. doi: 10.1021/acs.biochem.9b00365., Epub 2019 Aug 15. PMID:31355630 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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