5nde

Crystal structure of metallo-beta-lactamase SPM-1 in space group P4222

spinqualitylabelsall models 5nde, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5nde is a 2 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 1.7Å Ligands: CL, GOL, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8G9Q0_PSEAI Publication Abstract from PubMed The most important resistance mechanism to beta-lactam antibiotics involves hydrolysis by two beta-lactamase categories: the nucleophilic serine (SBL) and the metallo- (MBL) beta-lactamases. Cyclobutanones are hydrolytically stable beta-lactam analogues with potential to inhibit both SBLs and MBLs. We describe solution and crystallographic studies on the interaction of a cyclobutanone penem analogue with the clinically important MBL SPM-1. NMR experiments using 19F-labeled SPM-1 imply the cyclobutanone binds to SPM-1 with micromolar affinity. A crystal structure of the SPM-1:cyclobutanone complex reveals binding of the hydrated cyclobutanone via interactions with one of the zinc ions, stabilisation of the hydrate by hydrogen bonding to zinc-bound water, and hydrophobic contacts with aromatic residues. NMR analyses using a 13C-labeled cyclobutanone support assignment of the bound species as the hydrated ketone. The results inform on how MBLs bind substrates and stabilize tetrahedral intermediates. They support further investigations on the use of transition state and/or intermediate analogues as inhibitors of all beta-lactamase classes. Cyclobutanone Mimics of Intermediates in Metallo-beta-Lactamase Catalysis.,Abboud MI, Kosmopoulou M, Krismanich A, Johnson JW, Hinchliffe P, Brem J, Claridge TDW, Spencer J, Schofield C, Dmitrienko GI Chemistry. 2017 Dec 17. doi: 10.1002/chem.201705886. PMID:29250863 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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