1qw7 | pdb_00001qw7

Structure of an Engineered Organophosphorous Hydrolase with Increased Activity Toward Hydrolysis of Phosphothiolate Bonds

spinqualitylabelsall models 1qw7, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1qw7 is a 2 chain structure with sequence from Brevundimonas diminuta. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CO, EBP, NA NonStd Res: KCX Related: 1dpm Gene: OPD (Brevundimonas diminuta) Activity: Aryldialkylphosphatase, with EC number 3.1.8.1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Organophosphorus hydrolase detoxifies a broad range of organophosphate pesticides and the chemical warfare agents (CWAs) sarin and VX. Previously, rational genetic engineering produced OPH variants with 30-fold enhancements in the hydrolysis of CWA and their analogs. One interesting variant (H254R) in which the histidine at position 254 was changed to an arginine showed a 4-fold increase in the hydrolysis of demetonS (VX analog), a 14-fold decrease with paraoxon (an insecticide), and a 183-fold decrease with DFP (sarin analog). The three-dimensional structure of this enzyme at 1.9A resolution with the inhibitor, diethyl 4-methylbenzylphosphonate (EBP), revealed that the inhibitor did not bind at the active site, but bound exclusively into a well-defined surface pocket 12 A away from the active site. This structural feature was accompanied by non-competitive inhibition of paraoxon hydrolysis by EBP with H254R, in contrast to the native enzyme, which showed competitive inhibition. These parallel structure-function characteristics identify a functional, allosteric site on the surface of this enzyme. Structural and mutational studies of organophosphorus hydrolase reveal a cryptic and functional allosteric-binding site.,Grimsley JK, Calamini B, Wild JR, Mesecar AD Arch Biochem Biophys. 2005 Oct 15;442(2):169-79. Epub 2005 Sep 6. PMID:16188223 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotriesterase

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