4mll

The 1.4 A structure of the class D beta-lactamase OXA-1 K70D complexed with oxacillinThe 1.4 A structure of the class D beta-lactamase OXA-1 K70D complexed with oxacillin

Structural highlights 4mll is a 4 chain structure with sequence from Escherichia coli. This structure supersedes the now removed PDB entry 4f7y. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.37Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLO1_ECOLX This is an oxacillin-hydrolyzing beta-lactamase. Publication Abstract from PubMed Since the discovery and use of penicillin, the increase of antibiotic resistance among bacterial pathogens has become a major health concern. The most prevalent resistance mechanism in Gram-negative bacteria is due to beta-lactamase expression. Class D beta-lactamases are of particular importance due to their presence in multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. The class D enzymes were initially characterized by their ability to efficiently hydrolyze isoxazolyl-type beta-lactams like oxacillin. Due to this substrate preference, these enzymes are traditionally referred to as oxacillinases or OXAs. However, this class is comprised of subfamilies characterized by diverse activities that include oxacillinase, carbapenemase, or cephalosporinase substrate specificity. OXA-1 represents one subtype of class D enzyme that efficiently hydrolyzes oxacillin, and OXA-24/40 represents another with weak oxacillinase, but increased carbapenemase, activity. To examine the structural basis for the substrate selectivity differences between OXA-1 and OXA-24/40, the X-ray crystal structures of deacylation-deficient mutants of these enzymes (Lys70Asp for OXA-1; Lys84Asp for OXA-24) in complexes with oxacillin were determined to 1.4 A and 2.4 A, respectively. In the OXA-24/40/oxacillin structure, the hydrophobic R1 side chain of oxacillin disrupts the bridge between Tyr112 and Met223 present in the apo OXA-24/40 structure, causing the main chain of the Met223-containing loop to adopt a completely different conformation. In contrast, in the OXA-1/oxacillin structure, a hydrophobic pocket consisting of Trp102, Met99, Phe217, Leu161, and Leu255 nicely complements oxacillin's nonpolar R1 side chain. Comparison of the OXA-1/oxacillin and OXA-24/40/oxacillin complexes provides novel insight on how substrate selectivity is achieved among subtypes of class D beta-lactamases. By elucidating important active site interactions, these findings can also inform the design of novel antibiotics and inhibitors. Structural Origins of Oxacillinase Specificity in Class D beta-Lactamases.,June CM, Vallier BC, Bonomo RA, Leonard DA, Powers RA Antimicrob Agents Chemother. 2014 Jan;58(1):333-41. doi: 10.1128/AAC.01483-13., Epub 2013 Oct 28. PMID:24165180 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 4mll, resolution 1.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image