1fv0: Difference between revisions
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==FIRST STRUCTURAL EVIDENCE OF THE INHIBITION OF PHOSPHOLIPASE A2 BY ARISTOLOCHIC ACID: CRYSTAL STRUCTURE OF A COMPLEX FORMED BETWEEN PHOSPHOLIPASE A2 AND ARISTOLOCHIC ACID== | ==FIRST STRUCTURAL EVIDENCE OF THE INHIBITION OF PHOSPHOLIPASE A2 BY ARISTOLOCHIC ACID: CRYSTAL STRUCTURE OF A COMPLEX FORMED BETWEEN PHOSPHOLIPASE A2 AND ARISTOLOCHIC ACID== | ||
<StructureSection load='1fv0' size='340' side='right' caption='[[1fv0]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='1fv0' size='340' side='right'caption='[[1fv0]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1fv0]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1fv0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Daboia_russelii_pulchella Daboia russelii pulchella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FV0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FV0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AR:9-HYDROXY+ARISTOLOCHIC+ACID'>9AR</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9AR:9-HYDROXY+ARISTOLOCHIC+ACID'>9AR</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1fv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fv0 OCA], [https://pdbe.org/1fv0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fv0 RCSB], [https://www.ebi.ac.uk/pdbsum/1fv0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fv0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PA2B8_DABRR PA2B8_DABRR] Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:18062812</ref> <ref>PMID:2115497</ref> <ref>PMID:8835338</ref> | ||
== 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/fv/1fv0_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fv/1fv0_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1fv0 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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==See Also== | ==See Also== | ||
*[[Phospholipase A2|Phospholipase A2]] | *[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Daboia pulchella]] | [[Category: Daboia russelii pulchella]] | ||
[[Category: Betzel | [[Category: Large Structures]] | ||
[[Category: Chandra | [[Category: Betzel C]] | ||
[[Category: Jasti | [[Category: Chandra V]] | ||
[[Category: Kaur | [[Category: Jasti J]] | ||
[[Category: Singh | [[Category: Kaur P]] | ||
[[Category: Srinivasan | [[Category: Singh TP]] | ||
[[Category: Srinivasan A]] | |||
Latest revision as of 02:59, 21 November 2024
FIRST STRUCTURAL EVIDENCE OF THE INHIBITION OF PHOSPHOLIPASE A2 BY ARISTOLOCHIC ACID: CRYSTAL STRUCTURE OF A COMPLEX FORMED BETWEEN PHOSPHOLIPASE A2 AND ARISTOLOCHIC ACIDFIRST STRUCTURAL EVIDENCE OF THE INHIBITION OF PHOSPHOLIPASE A2 BY ARISTOLOCHIC ACID: CRYSTAL STRUCTURE OF A COMPLEX FORMED BETWEEN PHOSPHOLIPASE A2 AND ARISTOLOCHIC ACID
Structural highlights
FunctionPA2B8_DABRR Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.[1] [2] [3] 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 PubMedThis is the first structural observation of a plant product showing high affinity for phospholipase A(2) and regulating the synthesis of arachidonic acid, an intermediate in the production of prostaglandins. The crystal structure of a complex formed between Vipera russelli phospholipase A(2) and a plant alkaloid aristolochic acid has been determined and refined to 1.7 A resolution. The structure contains two crystallographically independent molecules of phospholipase A(2) in the form of an asymmetric dimer with one molecule of aristolochic acid bound to one of them specifically. The most significant differences introduced by asymmetric molecular association in the structures of two molecules pertain to the conformations of their calcium binding loops, beta-wings, and the C-terminal regions. These differences are associated with a unique conformational behavior of Trp(31). Trp(31) is located at the entrance of the characteristic hydrophobic channel which works as a passage to the active site residues in the enzyme. In the case of molecule A, Trp(31) is found at the interface of two molecules and it forms a number of hydrophobic interactions with the residues of molecule B. Consequently, it is pulled outwardly, leaving the mouth of the hydrophobic channel wide open. On the other hand, Trp(31) in molecule B is exposed to the surface and moves inwardly due to the polar environment on the molecular surface, thus narrowing the opening of the hydrophobic channel. As a result, the aristolochic acid is bound to molecule A only while the binding site of molecule B is empty. It is noteworthy that the most critical interactions in the binding of aristolochic acid are provided by its OH group which forms two hydrogen bonds, one each with His(48) and Asp(49). Structural basis of phospholipase A2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 A crystal structure.,Chandra V, Jasti J, Kaur P, Srinivasan A, Betzel Ch, Singh TP Biochemistry. 2002 Sep 10;41(36):10914-9. PMID:12206661[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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