Crystal Structure of DIM-1, an Acquired Subclass B1 Metallo-β-Lactamase from Pseudomonas stutzeri

Michael P S Booth, Magda Kosmopoulou, Laurent Poirel, Patrice Nordmann, Jim Spencer

Research output: Contribution to journalArticle (Academic Journal)

2 Citations (Scopus)

Abstract

Metallo-β-lactamases (MBLs) hydrolyze almost all classes of β-lactam antibiotic, including carbapenems-currently first choice drugs for opportunistic infections by Gram-negative bacterial pathogens. MBL inhibitor development is complicated by the diversity within this group of enzymes, and by the appearance of new enzymes that continue to be identified both as chromosomal genes and on mobile genetic elements. One such newly discovered MBL is DIM-1, a mobile enzyme originally discovered in the opportunist pathogen Pseudomonas stutzeri but subsequently identified in other species and locations. DIM-1 is a subclass B1 MBL more closely related to the TMB-1, GIM-1 and IMP enzymes than to other clinically encountered MBLs such as VIM and NDM; and possesses Arg, rather than the more usual Lys, at position 224 in the putative substrate binding site. Here we report the crystallization and structure determination of DIM-1. DIM-1 possesses a binuclear metal center with a 5 (rather than the more usual 4) co-ordinate tri-histidine (Zn1) site and both 4- and 5-co-ordinate Cys-His-Asp- (Zn2) sites observed in the two molecules of the crystallographic asymmetric unit. These data indicate a degree of variability in metal co-ordination geometry in the DIM-1 active site, as well as facilitating inclusion of DIM-1 in structure-based MBL inhibitor discovery programmes.

Original languageEnglish
Pages (from-to)e0140059
JournalPLoS ONE
Volume10
Issue number10
DOIs
Publication statusPublished - 2015

Keywords

  • Bacterial Proteins
  • Binding Sites
  • Crystallography
  • Histidine
  • Protein Conformation
  • Protein Isoforms
  • Pseudomonas stutzeri
  • Zinc
  • beta-Lactamases

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