Crystal Structure of DIM-1, an Acquired Subclass B1 Metallo-β-Lactamase from Pseudomonas stutzeri
- Booth, Michael P. S. School of Cellular and Molecular Medicine, University of Bristol Medical Sciences Building, University Walk, Bristol, United Kingdom
- Kosmopoulou, Magda School of Cellular and Molecular Medicine, University of Bristol Medical Sciences Building, University Walk, Bristol, United Kingdom
- Poirel, Laurent Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Switzerland
- Nordmann, Patrice Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Switzerland
- Spencer, James School of Cellular and Molecular Medicine, University of Bristol Medical Sciences Building, University Walk, Bristol, United Kingdom
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09.10.2015
Published in:
- PLoS ONE. - 2015, vol. 10, no. 10, p. e0140059
English
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Médecine 3ème année
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 258011
- DOI 10.1371/journal.pone.0140059
- Persistent URL
- https://folia.unifr.ch/unifr/documents/304697
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