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| | ==Crystal Structure of Bovin Brain Platelet Activating Factor Acetylhydrolase Covalently Inhibited by Sarin== | | ==Crystal Structure of Bovin Brain Platelet Activating Factor Acetylhydrolase Covalently Inhibited by Sarin== |
| - | <StructureSection load='3dt8' size='340' side='right' caption='[[3dt8]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='3dt8' size='340' side='right'caption='[[3dt8]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dt8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DT8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DT8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dt8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DT8 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SGB:O-[(S)-METHYL(1-METHYLETHOXY)PHOSPHORYL]-L-SERINE'>SGB</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]] 1.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wab|1wab]], [[3dt6|3dt6]], [[3dt9|3dt9]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SGB:O-[(S)-METHYL(1-METHYLETHOXY)PHOSPHORYL]-L-SERINE'>SGB</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAFAH1B3, PAFAHG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=3dt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dt8 OCA], [https://pdbe.org/3dt8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dt8 RCSB], [https://www.ebi.ac.uk/pdbsum/3dt8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dt8 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] </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=3dt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dt8 OCA], [http://pdbe.org/3dt8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dt8 RCSB], [http://www.ebi.ac.uk/pdbsum/3dt8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dt8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PA1B3_BOVIN PA1B3_BOVIN]] Inactivates paf by removing the acetyl group at the sn-2 position. This is a catalytic subunit. Plays an important role during the development of brain. | + | [https://www.uniprot.org/uniprot/PA1B3_BOVIN PA1B3_BOVIN] Inactivates paf by removing the acetyl group at the sn-2 position. This is a catalytic subunit. Plays an important role during the development of brain. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dt/3dt8_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dt/3dt8_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3dt8" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3dt8" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 1-alkyl-2-acetylglycerophosphocholine esterase]] | + | [[Category: Bos taurus]] |
| - | [[Category: Bovin]] | + | [[Category: Large Structures]] |
| - | [[Category: Bahnson, B J]] | + | [[Category: Bahnson BJ]] |
| - | [[Category: Epstein, T M]] | + | [[Category: Epstein TM]] |
| - | [[Category: Samanta, U]] | + | [[Category: Samanta U]] |
| - | [[Category: 26 kda]]
| + | |
| - | [[Category: Alpha-1 subunit]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Group viii phospholipase a2]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipid degradation]]
| + | |
| - | [[Category: Lis1]]
| + | |
| - | [[Category: Paf-ah ib]]
| + | |
| - | [[Category: Platelet activating factor acetylhydrolase]]
| + | |
| - | [[Category: Platelet factor]]
| + | |
| - | [[Category: Sarin]]
| + | |
| Structural highlights
Function
PA1B3_BOVIN Inactivates paf by removing the acetyl group at the sn-2 position. This is a catalytic subunit. Plays an important role during the development of brain.
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
Insecticide and nerve agent organophosphorus (OP) compounds are potent inhibitors of the serine hydrolase superfamily of enzymes. Nerve agents, such as sarin, soman, tabun, and VX exert their toxicity by inhibiting human acetycholinesterase at nerve synapses. Following the initial phosphonylation of the active site serine, the enzyme may reactivate spontaneously or through reaction with an appropriate nucleophilic oxime. Alternatively, the enzyme-nerve agent complex can undergo a secondary process, called "aging", which dealkylates the nerve agent adduct and results in a product that is highly resistant to reactivation by any known means. Here we report the structures of paraoxon, soman, and sarin complexes of group-VIII phospholipase A2 from bovine brain. In each case, the crystal structures indicate a nonaged adduct; a stereoselective preference for binding of the P(S)C(S) isomer of soman and the P(S) isomer of sarin was also noted. The stability of the nonaged complexes was corroborated by trypsin digest and electrospray ionization mass spectrometry, which indicates nonaged complexes are formed with diisopropylfluorophosphate, soman, and sarin. The P(S) stereoselectivity for reaction with sarin was confirmed by reaction of racemic sarin, followed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate each stereoisomer. The P(S) stereoisomers of soman and sarin are known to be the more toxic stereoisomers, as they react preferentially to inhibit human acetylcholinesterase. The results obtained for nonaged complexes of group-VIII phospholipase A2 are compared to those obtained for other serine hydrolases and discussed to partly explain determinants of OP aging. Furthermore, structural insights can now be exploited to engineer variant versions of this enzyme with enhanced nerve agent binding and hydrolysis functions.
Crystal structures of brain group-VIII phospholipase A2 in nonaged complexes with the organophosphorus nerve agents soman and sarin.,Epstein TM, Samanta U, Kirby SD, Cerasoli DM, Bahnson BJ Biochemistry. 2009 Apr 21;48(15):3425-35. PMID:19271773[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Epstein TM, Samanta U, Kirby SD, Cerasoli DM, Bahnson BJ. Crystal structures of brain group-VIII phospholipase A2 in nonaged complexes with the organophosphorus nerve agents soman and sarin. Biochemistry. 2009 Apr 21;48(15):3425-35. PMID:19271773 doi:10.1021/bi8023527
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