4zsu: Difference between revisions
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==Crystal structure of Brevundimonas diminuta phosphotriesterase mutant L7eP-3aG== | ==Crystal structure of Brevundimonas diminuta phosphotriesterase mutant L7eP-3aG== | ||
<StructureSection load='4zsu' size='340' side='right' caption='[[4zsu]], [[Resolution|resolution]] 2.01Å' scene=''> | <StructureSection load='4zsu' size='340' side='right'caption='[[4zsu]], [[Resolution|resolution]] 2.01Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4zsu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSU OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4zsu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Brevundimonas_diminuta Brevundimonas diminuta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZSU FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.011Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=4zsu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsu OCA], [https://pdbe.org/4zsu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zsu RCSB], [https://www.ebi.ac.uk/pdbsum/4zsu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsu ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/OPD_BREDI OPD_BREDI] Has an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates. All of the phosphate triesters found to be substrates are synthetic compounds. The identity of any naturally occurring substrate for the enzyme is unknown. Has no detectable activity with phosphate monoesters or diesters and no activity as an esterase or protease. It catalyzes the hydrolysis of the insecticide paraoxon at a rate approaching the diffusion limit and thus appears to be optimally evolved for utilizing this synthetic substrate. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4zsu" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphotriesterase 3D structures|Phosphotriesterase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Brevundimonas diminuta]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mabanglo MF]] | ||
[[Category: | [[Category: Raushel FM]] | ||
Latest revision as of 11:23, 27 September 2023
Crystal structure of Brevundimonas diminuta phosphotriesterase mutant L7eP-3aGCrystal structure of Brevundimonas diminuta phosphotriesterase mutant L7eP-3aG
Structural highlights
FunctionOPD_BREDI Has an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates. All of the phosphate triesters found to be substrates are synthetic compounds. The identity of any naturally occurring substrate for the enzyme is unknown. Has no detectable activity with phosphate monoesters or diesters and no activity as an esterase or protease. It catalyzes the hydrolysis of the insecticide paraoxon at a rate approaching the diffusion limit and thus appears to be optimally evolved for utilizing this synthetic substrate. Publication Abstract from PubMedThe V-type organophosphorus nerve agents are among the most hazardous compounds known. Previous efforts to evolve the bacterial enzyme phosphotriesterase (PTE) for the hydrolytic decontamination of VX resulted in the identification of the variant L7ep-3a, which has a kcat value more than 2 orders of magnitude higher than that of wild-type PTE for the hydrolysis of VX. Because of the relatively small size of the O-ethyl, methylphosphonate center in VX, stereoselectivity is not a major concern. However, the Russian V-agent, VR, contains a larger O-isobutyl, methylphosphonate center, making stereoselectivity a significant issue since the SP-enantiomer is expected to be significantly more toxic than the RP-enantiomer. The three-dimensional structure of the L7ep-3a variant was determined to a resolution of 2.01 A (PDB id: 4ZST ). The active site of the L7ep-3a mutant has revealed a network of hydrogen bonding interactions between Asp-301, Tyr-257, Gln-254, and the hydroxide that bridges the two metal ions. A series of new analogues that mimic VX and VR has helped to identify critical structural features for the development of new enzyme variants that are further enhanced for the catalytic detoxification of VR and VX. The best of these mutants has been shown to have a reversed stereochemical preference for the hydrolysis of VR-chiral center analogues. This mutant hydrolyzes the two enantiomers of VR 160- and 600-fold faster than wild-type PTE hydrolyzes the SP-enantiomer of VR. Variants of Phosphotriesterase for the Enhanced Detoxification of the Chemical Warfare Agent VR.,Bigley AN, Mabanglo MF, Harvey SP, Raushel FM Biochemistry. 2015 Aug 25. PMID:26274608[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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