3e3h: Difference between revisions
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==Crystal structure of the OP hydrolase mutant from Brevundimonas diminuta== | ==Crystal structure of the OP hydrolase mutant from Brevundimonas diminuta== | ||
<StructureSection load='3e3h' size='340' side='right' caption='[[3e3h]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='3e3h' size='340' side='right'caption='[[3e3h]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3e3h]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3e3h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aj_2067 Aj 2067]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E3H FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=EBP:DIETHYL+4-METHYLBENZYLPHOSPHONATE'>EBP</scene></td></tr> | </td></tr><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=EBP:DIETHYL+4-METHYLBENZYLPHOSPHONATE'>EBP</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">opd ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">opd ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=293 AJ 2067])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aryldialkylphosphatase Aryldialkylphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.8.1 3.1.8.1] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e3h OCA], [https://pdbe.org/3e3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e3h RCSB], [https://www.ebi.ac.uk/pdbsum/3e3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e3h ProSAT]</span></td></tr> | ||
</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. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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==See Also== | ==See Also== | ||
*[[Phosphotriesterase|Phosphotriesterase]] | *[[Phosphotriesterase 3D structures|Phosphotriesterase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Aj 2067]] | [[Category: Aj 2067]] | ||
[[Category: Aryldialkylphosphatase]] | [[Category: Aryldialkylphosphatase]] | ||
[[Category: Large Structures]] | |||
[[Category: Grimsley, J K]] | [[Category: Grimsley, J K]] | ||
[[Category: Li, P]] | [[Category: Li, P]] | ||
Revision as of 22:34, 20 October 2021
Crystal structure of the OP hydrolase mutant from Brevundimonas diminutaCrystal structure of the OP hydrolase mutant from Brevundimonas diminuta
Structural highlights
Function[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. 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 PubMedRational site-directed mutagenesis and biophysical analyses have been used to explore the thermodynamic stability and catalytic capabilities of organophosphorus hydrolase (OPH) and its genetically modified variants. There are clear trade-offs in the stability of modifications that enhance catalytic activities. For example, the H254R/H257L variant has higher turnover numbers for the chemical warfare agents VX (144 versus 14 s(-1) for the native enzyme (wild type) and VR (Russian VX, 465 versus 12 s(-1) for wild type). These increases are accompanied by a loss in stability in which the total Gibb's free energy for unfolding is 19.6 kcal/mol, which is 5.7 kcal/mol less than that of the wild-type enzyme. X-ray crystallographic studies support biophysical data that suggest amino acid residues near the active site contribute to the chemical and thermal stability through hydrophobic and cation-pi interactions. The cation-pi interactions appear to contribute an additional 7 kcal/mol to the overall global stability of the enzyme. Using rational design, it has been possible to make amino acid changes in this region that restored the stability, yet maintained effective V-agent activities, with turnover numbers of 68 and 36 s(-1) for VX and VR, respectively. This study describes the first rationally designed, stability/activity balance for an OPH enzyme with a legitimate V-agent activity, and its crystal structure. Balancing the stability and the catalytic specificities of OP hydrolases with enhanced V-agent activities.,Reeves TE, Wales ME, Grimsley JK, Li P, Cerasoli DM, Wild JR Protein Eng Des Sel. 2008 Jun;21(6):405-12. Epub 2008 Apr 23. PMID:18434422[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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