6NZ8

Structure of carbamylated apo OXA-231 carbapenemase

Summary for 6NZ8

• Entry DOI: 10.2210/pdb6nz8/pdb
• Descriptor: Beta-lactamase OXA-231, SODIUM ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: beta-lactamase, oxacillinase, oxa-143 subgroup, carbapenemase, hydrolase
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 1
• Total formula weight: 29600.57

Authors

Favaro, D.C.,Llontop, E.E.,Vasconcelos, F.N.,Antunes, V.U.,Farah, S.C.,Lincopan, N. (deposition date: 2019-02-13, release date: 2020-02-19, Last modification date: 2023-11-15)

Primary citation

Antunes, V.U.,Llontop, E.E.,Vasconcelos, F.N.D.C.,Lopez de Los Santos, Y.,Oliveira, R.J.,Lincopan, N.,Farah, C.S.,Doucet, N.,Mittermaier, A.,Favaro, D.C.
Importance of the beta 5-beta 6 Loop for the Structure, Catalytic Efficiency, and Stability of Carbapenem-Hydrolyzing Class D beta-Lactamase Subfamily OXA-143.
Biochemistry, 58:3604-3616, 2019

PubMed Abstract: The class D β-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 ) and a higher turnover number (higher ). 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.

PubMed: 31355630
DOI: 10.1021/acs.biochem.9b00365

Experimental method

X-RAY DIFFRACTION (1.2 Å)