1mf4

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(New page: 200px<br /><applet load="1mf4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mf4, resolution 1.90&Aring;" /> '''Structure-based desi...)
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[[Image:1mf4.jpg|left|200px]]<br /><applet load="1mf4" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1mf4, resolution 1.90&Aring;" />
 
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'''Structure-based design of potent and selective inhibitors of phospholipase A2: Crystal structure of the complex formed between phosholipase A2 from Naja Naja sagittifera and a designed peptide inhibitor at 1.9 A resolution'''<br />
 
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==Overview==
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==Structure-based design of potent and selective inhibitors of phospholipase A2: Crystal structure of the complex formed between phosholipase A2 from Naja Naja sagittifera and a designed peptide inhibitor at 1.9 A resolution==
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Phospholipase A(2) (PLA(2)) (E. C. 3.1.1.4) is a common enzyme in the, two-way cascade mechanism leading to the production of proinflammatory, compounds known as eicosanoids. The binding of phospholipase A(2) to the, membrane surface and hydrolysis of phospholipids are thought to involve, the formation of a hydrophobic channel into which a single substrate, molecule diffuses before its cleavage. To regulate the production of, proinflammatory compounds, a specific peptide inhibitor, Val-Ala-Phe-Arg-Ser (VAFRS) for the group I PLA(2) enzymes has been, designed and synthesized. PLA(2) was isolated from Indian cobra (Naja naja, sagittifera) venom and purified to homogeneity. The binding studies, indicated the K(i) value of 1.02 +/- 0.10 x 10(-8) M. The purified PLA(2), samples and the designed inhibitor VAFRS were cocrystallized. The crystal, structure of the complex was determined and refined to 1.9 A resolution., The peptide binds to PLA(2) at the active site and fills the hydrophobic, channel completely. However, its placement with respect to the channel is, in the opposite direction as compared to those observed in group II, PLA(2)'s. Furthermore, the predominant intermolecular interactions involve, strong electrostatic interactions between the side chains of peptide Arg, and Asp 49 of PLA(2) together with a number of van der Waals interactions, with other residues. A good number of observed interactions between the, peptide and the protein indicate the significance of a structure-based, drug design approach. The novel factor in the present sequence of the, peptide is related to the introduction of a positively charged residue at, the C-terminal part of the peptide.
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<StructureSection load='1mf4' size='340' side='right'caption='[[1mf4]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1mf4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_sagittifera Naja sagittifera]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MF4 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mf4 OCA], [https://pdbe.org/1mf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mf4 RCSB], [https://www.ebi.ac.uk/pdbsum/1mf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mf4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PA2A3_NAJSG PA2A3_NAJSG] PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mf/1mf4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1mf4 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1MF4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Naja_sagittifera Naja sagittifera] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MF4 OCA].
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*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Design of specific peptide inhibitors for group I phospholipase A2: structure of a complex formed between phospholipase A2 from Naja naja sagittifera (group I) and a designed peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) at 1.9 A resolution reveals unique features., Singh RK, Vikram P, Makker J, Jabeen T, Sharma S, Dey S, Kaur P, Srinivasan A, Singh TP, Biochemistry. 2003 Oct 14;42(40):11701-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14529280 14529280]
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[[Category: Large Structures]]
[[Category: Naja sagittifera]]
[[Category: Naja sagittifera]]
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[[Category: Phospholipase A(2)]]
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[[Category: Dey S]]
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[[Category: Single protein]]
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[[Category: Jabeen T]]
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[[Category: Dey, S.]]
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[[Category: Kaur P]]
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[[Category: Jabeen, T.]]
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[[Category: Makker J]]
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[[Category: Kaur, P.]]
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[[Category: Paramsivam M]]
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[[Category: Makker, J.]]
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[[Category: Sharma S]]
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[[Category: Paramsivam, M.]]
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[[Category: Singh RK]]
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[[Category: Sharma, S.]]
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[[Category: Singh TP]]
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[[Category: Singh, R.K.]]
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[[Category: Srinivasan A]]
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[[Category: Singh, T.P.]]
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[[Category: Vikram P]]
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[[Category: Srinivasan, A.]]
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[[Category: Vikram, P.]]
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[[Category: CA]]
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[[Category: designed inhibitor]]
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[[Category: naja naja sagittifera]]
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[[Category: phospholipase a2]]
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[[Category: structure]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:22:55 2007''
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Current revision

Structure-based design of potent and selective inhibitors of phospholipase A2: Crystal structure of the complex formed between phosholipase A2 from Naja Naja sagittifera and a designed peptide inhibitor at 1.9 A resolution

PDB ID 1mf4

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