2oul
From Proteopedia
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| - | [[Image:2oul.png|left|200px]] | ||
| - | + | ==The Structure of Chagasin in Complex with a Cysteine Protease Clarifies the Binding Mode and Evolution of a New Inhibitor Family== | |
| + | <StructureSection load='2oul' size='340' side='right'caption='[[2oul]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2oul]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7] and [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OUL FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</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=2oul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oul OCA], [https://pdbe.org/2oul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oul RCSB], [https://www.ebi.ac.uk/pdbsum/2oul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oul ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FPC2A_PLAF7 FPC2A_PLAF7] Cysteine protease which cleaves native host hemoglobin and globin in the food vacuole during the asexual blood stage (PubMed:10887194, PubMed:15070727, PubMed:15964982, PubMed:16777845, PubMed:19357776, PubMed:25791019). The binding to host hemoglobin is pH-sensitive and only occurs at acidic pH (PubMed:16777845). Cleaves ankyrin and protein 4.1, two components of host erythrocyte membrane cytoskeleton required for the stability of the erythrocyte membrane, and thus may be involved in parasite release (PubMed:11463472). Preferentially cleaves substrates which have an arginine or lysine at the P1 position and a leucine or phenylalanine at the P2 position (PubMed:10887194, PubMed:19357776).<ref>PMID:10887194</ref> <ref>PMID:11463472</ref> <ref>PMID:15070727</ref> <ref>PMID:15964982</ref> <ref>PMID:16777845</ref> <ref>PMID:19357776</ref> <ref>PMID:25791019</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ou/2oul_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </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/main_output.php?pdb_ID=2oul ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Protein inhibitors of proteolytic enzymes regulate proteolysis and prevent the pathological effects of excess endogenous or exogenous proteases. Cysteine proteases are a large family of enzymes found throughout the plant and animal kingdoms. Disturbance of the equilibrium between cysteine proteases and natural inhibitors is a key event in the pathogenesis of cancer, rheumatoid arthritis, osteoporosis, and emphysema. A family (I42) of cysteine protease inhibitors (http://merops.sanger.ac.uk) was discovered in protozoan parasites and recently found widely distributed in prokaryotes and eukaryotes. We report the 2.2 A crystal structure of the signature member of the I42 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8alpha. Interactions of chagasin with a target protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of cysteine proteases may have evolved more than once on nonhomologous scaffolds. | ||
| - | + | The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family.,Wang SX, Pandey KC, Scharfstein J, Whisstock J, Huang RK, Jacobelli J, Fletterick RJ, Rosenthal PJ, Abrahamson M, Brinen LS, Rossi A, Sali A, McKerrow JH Structure. 2007 May;15(5):535-43. PMID:17502099<ref>PMID:17502099</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2oul" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | == | + | __TOC__ |
| - | < | + | </StructureSection> |
| - | [[Category: Plasmodium falciparum]] | + | [[Category: Large Structures]] |
| + | [[Category: Plasmodium falciparum 3D7]] | ||
[[Category: Trypanosoma cruzi]] | [[Category: Trypanosoma cruzi]] | ||
| - | [[Category: Chand | + | [[Category: Chand K]] |
| - | [[Category: Fletterick | + | [[Category: Fletterick RJ]] |
| - | [[Category: Huang | + | [[Category: Huang R]] |
| - | [[Category: Jacobelli | + | [[Category: Jacobelli J]] |
| - | [[Category: McKerrow | + | [[Category: McKerrow JH]] |
| - | [[Category: Rosenthal | + | [[Category: Rosenthal PJ]] |
| - | [[Category: Wang | + | [[Category: Wang SX]] |
| - | [[Category: Whisstock | + | [[Category: Whisstock J]] |
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Current revision
The Structure of Chagasin in Complex with a Cysteine Protease Clarifies the Binding Mode and Evolution of a New Inhibitor Family
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