View source for 4zwu


==Crystal structure of organophosphate anhydrolase/prolidase mutant Y212F, V342L, I215Y==
<StructureSection load='4zwu' size='340' side='right'caption='[[4zwu]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zwu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Alteromonas_sp. Alteromonas sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZWU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene>, <scene name='pdbligand=GOA:GLYCOLIC+ACID'>GOA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zwu OCA], [https://pdbe.org/4zwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zwu RCSB], [https://www.ebi.ac.uk/pdbsum/4zwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zwu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PEPQ_ALTSX 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.<ref>PMID:8633861</ref> <ref>PMID:2001997</ref> <ref>PMID:9079288</ref> <ref>PMID:10866401</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:26418828</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zwu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Alteromonas sp]]
[[Category: Large Structures]]
[[Category: Daczkowski CM]]
[[Category: Harvey SP]]
[[Category: Pegan SD]]