5FDH

CRYSTAL STRUCTURE OF OXA-405 BETA-LACTAMASE

Summary for 5FDH

• Entry DOI: 10.2210/pdb5fdh/pdb
• Descriptor: Beta-lactamase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: class d beta-lactamase oxa-405, antibiotic, hydrolase
• Biological source: Serratia marcescens
• Total number of polymer chains: 2
• Total formula weight: 59746.97

Authors

Retailleau, P.,Oueslati, S.,Marchini, L.,Dortet, L.,Naas, T.,Iorga, B. (deposition date: 2015-12-16, release date: 2016-12-28, Last modification date: 2024-01-10)

Primary citation

Oueslati, S.,Retailleau, P.,Marchini, L.,Dortet, L.,Bonnin, R.A.,Iorga, B.I.,Naas, T.
Biochemical and Structural Characterization of OXA-405, an OXA-48 Variant with Extended-Spectrum beta-Lactamase Activity.
Microorganisms, 8:-, 2019

PubMed Abstract: OXA-48-producing Enterobacterales have now widely disseminated globally. A sign of their extensive spread is the identification of an increasing number of OXA-48 variants. Among them, three are particularly interesting, OXA-163, OXA-247 and OXA-405, since they have lost carbapenem activities and gained expanded-spectrum cephalosporin hydrolytic activity subsequent to a four amino-acid (AA) deletion in the β5-β6 loop. We investigated the mechanisms responsible for substrate specificity of OXA-405. Kinetic parameters confirmed that OXA-405 has a hydrolytic profile compatible with an ESBL (hydrolysis of expanded spectrum cephalosporins and susceptibility to class A inhibitors). Molecular modeling techniques and 3D structure determination show that the overall dimeric structure of OXA-405 is very similar to that of OXA-48, except for the β5-β6 loop, which is shorter for OXA-405, suggesting that the length of the β5-β6 loop is critical for substrate specificity. Covalent docking with selected substrates and molecular dynamics simulations evidenced the structural changes induced by substrate binding, as well as the distribution of water molecules in the active site and their role in substrate hydrolysis. All this data may represent the structural basis for the design of new and efficient class D inhibitors.

PubMed: 31877796
DOI: 10.3390/microorganisms8010024

Experimental method

X-RAY DIFFRACTION (2.26 Å)