2ynt

GIM-1-3Mol native. Crystal structures of Pseudomonas aeruginosa GIM- 1: active site plasticity in metallo-beta-lactamases

spinqualitylabelsall models 2ynt, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ynt is a 3 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.598Å Ligands: GOL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q704V1_PSEAI Publication Abstract from PubMed Metallo-beta-lactamases (MBLs) have rapidly disseminated worldwide among clinically important Gram-negative bacteria and have challenged the therapeutic use of beta-lactam antibiotics, particularly carbapenems. The bla(GIM-1) gene, encoding one such enzyme, was first discovered in a Pseudomonas aeruginosa isolate from 2002 and has more recently been reported in Enterobacteriaceae. Here, we present crystal structures of GIM-1 in the apo-zinc (metal-free), mono-zinc (where Cys221 was found to be oxidized), and di-zinc forms, providing nine independently refined views of the enzyme. GIM-1 is distinguished from related MBLs in possessing a narrower active-site groove defined by aromatic side chains (Trp228 and Tyr233) at positions normally occupied by hydrophilic residues in other MBLs. Our structures reveal considerable flexibility in two loops (loop 1, residues 60 to 66; loop 2, residues 223 to 242) adjacent to the active site, with open and closed conformations defined by alternative hydrogen-bonding patterns involving Trp228. We suggest that this capacity for rearrangement permits GIM-1 to hydrolyze a wide range of beta-lactams in spite of possessing a more constrained active site. Our results highlight the structural diversity within the MBL enzyme family. Crystal structures of Pseudomonas aeruginosa GIM-1: active-site plasticity in metallo-beta-lactamases.,Borra PS, Samuelsen O, Spencer J, Walsh TR, Lorentzen MS, Leiros HK Antimicrob Agents Chemother. 2013 Feb;57(2):848-54. doi: 10.1128/AAC.02227-12., Epub 2012 Dec 3. PMID:23208706 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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