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3l24

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Revision as of 10:51, 25 December 2014

Crystal Structure of the Nerve Agent Degrading Organophosphate Anhydrolase/Prolidase in Complex with Inhibitors

Structural highlights

3l24 is a 3 chain structure with sequence from Alteromonas sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	opaA, pepQ (Alteromonas sp.)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3l24"

@@ Line 7: / Line 7: @@
 <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=3l24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l24 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l24 RCSB], [http://www.ebi.ac.uk/pdbsum/3l24 PDBsum]</span></td></tr>
 </table>
+== 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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3l24

From Proteopedia

Revision as of 10:51, 25 December 2014

Crystal Structure of the Nerve Agent Degrading Organophosphate Anhydrolase/Prolidase in Complex with Inhibitors

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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