1yvb

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(New page: 200px<br /> <applet load="1yvb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yvb, resolution 2.70&Aring;" /> '''the Plasmodium falc...)
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[[Image:1yvb.gif|left|200px]]<br />
 
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<applet load="1yvb" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1yvb, resolution 2.70&Aring;" />
 
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'''the Plasmodium falciparum Cysteine Protease Falcipain-2'''<br />
 
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==Overview==
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==the Plasmodium falciparum Cysteine Protease Falcipain-2==
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Falcipain-2 (FP2), the major cysteine protease of the human malaria, parasite Plasmodium falciparum, is a hemoglobinase and promising drug, target. Here we report the crystal structure of FP2 in complex with a, protease inhibitor, cystatin. The FP2 structure reveals two previously, undescribed cysteine protease structural motifs, designated FP2(nose) and, FP2(arm), in addition to details of the active site that will help focus, inhibitor design. Unlike most cysteine proteases, FP2 does not require a, prodomain but only the short FP2(nose) motif to correctly fold and gain, catalytic activity. Our structure and mutagenesis data suggest a molecular, basis for this unique mechanism by highlighting the functional role of two, Tyr within FP2(nose) and a conserved Glu outside this motif. The FP2(arm), motif is required for hemoglobinase activity. The structure reveals, topographic features and a negative charge cluster surrounding FP2(arm), that suggest it may serve as an exo-site for hemoglobin binding. Motifs, similar to FP2(nose) and FP2(arm) are found only in related plasmodial, proteases, suggesting that they confer malaria-specific functions.
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<StructureSection load='1yvb' size='340' side='right'caption='[[1yvb]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1yvb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YVB 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]] 2.7&#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=GOL:GLYCEROL'>GOL</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=1yvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yvb OCA], [https://pdbe.org/1yvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yvb RCSB], [https://www.ebi.ac.uk/pdbsum/1yvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yvb ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q9N6S8_PLAFA Q9N6S8_PLAFA]
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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/yv/1yvb_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=1yvb ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Falcipain-2 (FP2), the major cysteine protease of the human malaria parasite Plasmodium falciparum, is a hemoglobinase and promising drug target. Here we report the crystal structure of FP2 in complex with a protease inhibitor, cystatin. The FP2 structure reveals two previously undescribed cysteine protease structural motifs, designated FP2(nose) and FP2(arm), in addition to details of the active site that will help focus inhibitor design. Unlike most cysteine proteases, FP2 does not require a prodomain but only the short FP2(nose) motif to correctly fold and gain catalytic activity. Our structure and mutagenesis data suggest a molecular basis for this unique mechanism by highlighting the functional role of two Tyr within FP2(nose) and a conserved Glu outside this motif. The FP2(arm) motif is required for hemoglobinase activity. The structure reveals topographic features and a negative charge cluster surrounding FP2(arm) that suggest it may serve as an exo-site for hemoglobin binding. Motifs similar to FP2(nose) and FP2(arm) are found only in related plasmodial proteases, suggesting that they confer malaria-specific functions.
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==About this Structure==
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Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease.,Wang SX, Pandey KC, Somoza JR, Sijwali PS, Kortemme T, Brinen LS, Fletterick RJ, Rosenthal PJ, McKerrow JH Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11503-8. Epub 2006 Jul 24. PMID:16864794<ref>PMID:16864794</ref>
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1YVB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [http://en.wikipedia.org/wiki/Plasmodium_falciparum_3d7 Plasmodium falciparum 3d7] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YVB OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease., Wang SX, Pandey KC, Somoza JR, Sijwali PS, Kortemme T, Brinen LS, Fletterick RJ, Rosenthal PJ, McKerrow JH, Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11503-8. Epub 2006 Jul 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16864794 16864794]
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</div>
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<div class="pdbe-citations 1yvb" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
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[[Category: Plasmodium falciparum 3d7]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Plasmodium falciparum 3D7]]
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[[Category: Wang, S.X.]]
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[[Category: Wang SX]]
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[[Category: GOL]]
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[[Category: cysteine protease-inhibitor complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov 8 13:27:29 2007''
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Current revision

the Plasmodium falciparum Cysteine Protease Falcipain-2

PDB ID 1yvb

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