5wcm | pdb_00005wcm

Crystal structure of the complex between class B3 beta-lactamase BJP-1 and 4-nitrobenzene-sulfonamide - new refinement

spinqualitylabelsall models 5wcm, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5wcm is a 2 chain structure with sequence from Bradyrhizobium diazoefficiens USDA 110. This structure supersedes the now removed PDB entry 3m8t. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.2Å Ligands: 4NZ, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q89GW5_BRADU Publication Abstract from PubMed Metallo-beta-lactamases (MBLs) are important enzymatic factors in resistance to beta-lactam antibiotics that show important structural and functional heterogeneity. BJP-1 is a subclass B3 MBL determinant produced by Bradyrhizobium japonicum that exhibits interesting properties. BJP-1, like CAU-1 of Caulobacter vibrioides, overall poorly recognizes beta-lactam substrates and shows an unusual substrate profile compared to other MBLs. In order to understand the structural basis of these properties, the crystal structure of BJP-1 was obtained at 1.4-A resolution. This revealed significant differences in the conformation and locations of the active-site loops, determining a rather narrow active site and the presence of a unique N-terminal helix bearing Phe-31, whose side chain binds in the active site and represents an obstacle for beta-lactam substrate binding. In order to probe the potential of sulfonamides (known to inhibit various zinc-dependent enzymes) to bind in the active sites of MBLs, the structure of BJP-1 in complex with 4-nitrobenzenesulfonamide was also obtained (at 1.33-A resolution), thereby revealing the mode of interaction of these molecules in MBLs. Interestingly, sulfonamide binding resulted in the displacement of the side chain of Phe-31 from its hydrophobic binding pocket, where the benzene ring of the molecule is now found. These data further highlight the structural diversity shown by MBLs but also provide interesting insights in the structure-function relationships of these enzymes. More importantly, we provided the first structural observation of MBL interaction with sulfonamides, which might represent an interesting scaffold for the design of MBL inhibitors. High-resolution crystal structure of the subclass B3 metallo-beta-lactamase BJP-1: rational basis for substrate specificity and interaction with sulfonamides.,Docquier JD, Benvenuti M, Calderone V, Stoczko M, Menciassi N, Rossolini GM, Mangani S Antimicrob Agents Chemother. 2010 Oct;54(10):4343-51. Epub 2010 Aug 9. PMID:20696874 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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