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| | ==Crystal structure of organophosphate anhydrolase/prolidase== | | ==Crystal structure of organophosphate anhydrolase/prolidase== |
| - | <StructureSection load='3l7g' size='340' side='right' caption='[[3l7g]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3l7g' size='340' side='right'caption='[[3l7g]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3l7g]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Altsx Altsx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L7G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3l7g]] is a 3 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=3L7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L7G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M44:N,N-BIS(1-METHYLETHYL)PHOSPHORODIAMIDIC+ACID'>M44</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l24|3l24]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">opaA, pepQ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=232 ALTSX])</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=3l7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l7g OCA], [https://pdbe.org/3l7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l7g RCSB], [https://www.ebi.ac.uk/pdbsum/3l7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l7g ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l7g OCA], [http://pdbe.org/3l7g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l7g RCSB], [http://www.ebi.ac.uk/pdbsum/3l7g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l7g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Altsx]] | + | [[Category: Alteromonas sp]] |
| - | [[Category: Nickitenko, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Quiocho, F A]] | + | [[Category: Nickitenko A]] |
| - | [[Category: Vyas, N K]] | + | [[Category: Quiocho FA]] |
| - | [[Category: Detoxification]] | + | [[Category: Vyas NK]] |
| - | [[Category: Dipeptidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Manganese]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Pita-bread]]
| + | |
| - | [[Category: Protease]]
| + | |
| Structural highlights
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.[1] [2] [3] [4]
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 PubMed
The organophosphate acid anhydrolase (OPAA) is a member of a class of bimetalloenzymes that hydrolyze a variety of toxic acetylcholinesterase-inhibiting organophosphorus compounds, including fluorine-containing chemical nerve agents. It also belongs to a family of prolidases, with significant activity against various Xaa-Pro dipeptides. Here we report the X-ray structure determination of the native OPAA (58 kDa mass) from Alteromonas sp. strain JD6.5 and its cocrystal with the inhibitor mipafox [N,N'-diisopropyldiamidofluorophosphate (DDFP)], a close analogue of the nerve agent organophosphate substrate diisopropyl fluorophosphate (DFP). The OPAA structure is composed of two domains, amino and carboxy domains, with the latter exhibiting a "pita bread" architecture and harboring the active site with the binuclear Mn(2+) ions. The native OPAA structure revealed unexpectedly the presence of a well-defined nonproteinaceous density in the active site whose identity could not be definitively established but is suggestive of a bound glycolate, which is isosteric with a glycine (Xaa) product. All three glycolate oxygens coordinate the two Mn(2+) atoms. DDFP or more likely its hydrolysis product, N,N'-diisopropyldiamidophosphate (DDP), is present in the cocrystal structure and bound by coordinating the binuclear metals and forming hydrogen bonds and nonpolar interactions with active site residues. An unusual common feature of the binding of the two ligands is the involvement of only one oxygen atom of the glycolate carboxylate and the product DDP tetrahedral phosphate in bridging the two Mn(2+) ions. Both structures provide new understanding of ligand recognition and the prolidase and organophosphorus hydrolase catalytic activities of OPAA.
Structural insights into the dual activities of the nerve agent degrading organophosphate anhydrolase/prolidase.,Vyas NK, Nickitenko A, Rastogi VK, Shah SS, Quiocho FA Biochemistry. 2010 Jan 26;49(3):547-59. PMID:20000741[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cheng TC, Harvey SP, Chen GL. Cloning and expression of a gene encoding a bacterial enzyme for decontamination of organophosphorus nerve agents and nucleotide sequence of the enzyme. Appl Environ Microbiol. 1996 May;62(5):1636-41. PMID:8633861
- ↑ DeFrank JJ, Cheng TC. Purification and properties of an organophosphorus acid anhydrase from a halophilic bacterial isolate. J Bacteriol. 1991 Mar;173(6):1938-43. PMID:2001997
- ↑ Cheng T, Liu L, Wang B, Wu J, DeFrank JJ, Anderson DM, Rastogi VK, Hamilton AB. Nucleotide sequence of a gene encoding an organophosphorus nerve agent degrading enzyme from Alteromonas haloplanktis. J Ind Microbiol Biotechnol. 1997 Jan;18(1):49-55. PMID:9079288
- ↑ Hill CM, Wu F, Cheng TC, DeFrank JJ, Raushel FM. Substrate and stereochemical specificity of the organophosphorus acid anhydrolase from Alteromonas sp. JD6.5 toward p-nitrophenyl phosphotriesters. Bioorg Med Chem Lett. 2000 Jun 5;10(11):1285-8. PMID:10866401
- ↑ Vyas NK, Nickitenko A, Rastogi VK, Shah SS, Quiocho FA. Structural insights into the dual activities of the nerve agent degrading organophosphate anhydrolase/prolidase. Biochemistry. 2010 Jan 26;49(3):547-59. PMID:20000741 doi:10.1021/bi9011989
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