4zwp: Difference between revisions
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==Crystal structure of organophosphate anhydrolase/prolidase mutant Y212F== | |||
<StructureSection load='4zwp' size='340' side='right'caption='[[4zwp]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4zwp]] 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=4ZWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZWP 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]] 2.397Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M44:N,N-BIS(1-METHYLETHYL)PHOSPHORODIAMIDIC+ACID'>M44</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=4zwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zwp OCA], [https://pdbe.org/4zwp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zwp RCSB], [https://www.ebi.ac.uk/pdbsum/4zwp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zwp 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4zwp" style="background-color:#fffaf0;"></div> | ||
[[Category: Daczkowski | == References == | ||
[[Category: Harvey | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Alteromonas sp]] | |||
[[Category: Large Structures]] | |||
[[Category: Daczkowski CM]] | |||
[[Category: Harvey SP]] | |||
[[Category: Pegan SD]] | |||
