4zwp

Crystal structure of organophosphate anhydrolase/prolidase mutant Y212F

spinqualitylabelsall models 4zwp, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zwp is a 2 chain structure with sequence from Alteromonas sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.397Å Ligands: BA, GOL, M44, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PEPQ_ALTSX Splits dipeptides with a prolyl or hydroxyprolyl residue in the C-terminal position and a nonpolar amino acid at the N-terminal position. Also catalyzes the hydrolysis of toxic organophosphorus cholinesterase-inhibiting compounds including insecticide paraoxon and nerve gases such as diisopropylfluorophosphate (DFP), O-isopropyl methylphosphonofluoridate (sarin), O-pinacolyl methylphosphonofluoridate (soman), and O-cyclohexyl methylphosphonofluoridate. Publication Abstract from PubMed The enzyme organophosphorus acid anhydrolase (OPAA), from Alteromonas sp. JD6.5, has been shown to rapidly catalyze the hydrolysis of a number of toxic organophosphorus compounds, including several G-type chemical nerve agents. The enzyme was cloned into Escherichia coli and can be produced up to approximately 50% of cellular protein. There have been no previous reports of OPAA activity on VR {Russian VX, O-isobutyl S-[2-(diethylamino)ethyl] methylphosphonothioate}, and our studies reported here show that wild-type OPAA has poor catalytic efficacy toward VR. However, via application of a structurally aided protein engineering approach, significant improvements in catalytic efficiency were realized via optimization of the small pocket within the OPAA's substrate-binding site. This optimization involved alterations at only three amino acid sites resulting in a 30-fold increase in catalytic efficiency toward racemic VR, with a strong stereospecificity toward the P(+) enantiomer. X-ray structures of this mutant as well as one of its predecessors provide potential structural rationales for their effect on the OPAA active site. Additionally, a fourth mutation at a site near the small pocket was found to relax the stereospecificity of the OPAA enzyme. Thus, it allows the altered enzyme to effectively process both VR enantiomers and should be a useful genetic background in which to seek further improvements in OPAA VR activity. Engineering the Organophosphorus Acid Anhydrolase Enzyme for Increased Catalytic Efficiency and Broadened Stereospecificity on Russian VX.,Daczkowski CM, Pegan SD, Harvey SP Biochemistry. 2015 Oct 6. PMID:26418828 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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