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| - | ==PROLINE RACEMASE IN COMPLEX WITH ONE MOLECULE OF PYRROLE-2-CARBOXYLIC ACID (HEMI FORM)== | + | |
| - | <StructureSection load='1w62' size='340' side='right' caption='[[1w62]], [[Resolution|resolution]] 2.50Å' scene=''> | + | ==proline racemase in complex with one molecule of pyrrole-2-carboxylic acid (hemi form)== |
| | + | <StructureSection load='1w62' size='340' side='right'caption='[[1w62]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1w62]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W62 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W62 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1w62]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi_strain_CL_Brener Trypanosoma cruzi strain CL Brener]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W62 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PYC:PYRROLE-2-CARBOXYLATE'>PYC</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]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1w61|1w61]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PYC:PYRROLE-2-CARBOXYLATE'>PYC</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proline_racemase Proline racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.4 5.1.1.4] </span></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=1w62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w62 OCA], [https://pdbe.org/1w62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w62 RCSB], [https://www.ebi.ac.uk/pdbsum/1w62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w62 ProSAT]</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=1w62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w62 OCA], [http://pdbe.org/1w62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w62 RCSB], [http://www.ebi.ac.uk/pdbsum/1w62 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PRCMA_TRYCC PRCMA_TRYCC] Catalyzes the interconversion of L- and D-proline. Secreted isoform 1 contributes to parasite immune evasion by acting as a B-cell mitogen. Probably involved in parasite differentiation and infectivity.<ref>PMID:10932226</ref> <ref>PMID:16164548</ref> <ref>PMID:16446443</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/w6/1w62_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w6/1w62_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> |
| | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=1w62 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Proline racemase]] | + | [[Category: Large Structures]] |
| - | [[Category: Trycr]] | + | [[Category: Trypanosoma cruzi strain CL Brener]] |
| - | [[Category: Alzari, P]] | + | [[Category: Alzari P]] |
| - | [[Category: Buschiazzo, A]] | + | [[Category: Buschiazzo A]] |
| - | [[Category: Alpha/beta domain]]
| + | |
| - | [[Category: B-cell mitogen]]
| + | |
| - | [[Category: Homodimer]]
| + | |
| - | [[Category: Racemase]]
| + | |
| - | [[Category: Racemase pyridoxal phosphate-independent]]
| + | |
| - | [[Category: Stereo inversion]]
| + | |
| Structural highlights
Function
PRCMA_TRYCC Catalyzes the interconversion of L- and D-proline. Secreted isoform 1 contributes to parasite immune evasion by acting as a B-cell mitogen. Probably involved in parasite differentiation and infectivity.[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 PubMed
Amino acid racemases catalyze the stereoinversion of the chiral C alpha to produce the d-enantiomers that participate in biological processes, such as cell wall construction in prokaryotes. Within this large protein family, bacterial proline racemases have been extensively studied as a model of enzymes acting with a pyridoxal-phosphate-independent mechanism. Here we report the crystal structure of the proline racemase from the human parasite Trypanosoma cruzi (TcPRACA), a secreted enzyme that triggers host B cell polyclonal activation, which prevents specific humoral immune responses and is crucial for parasite evasion and fate. The enzyme is a homodimer, with each monomer folded in two symmetric alpha/beta subunits separated by a deep crevice. The structure of TcPRACA in complex with a transition-state analog, pyrrole-2-carboxylic acid, reveals the presence of one reaction center per monomer, with two Cys residues optimally located to perform acid/base catalysis through a carbanion stabilization mechanism. Mutation of the catalytic Cys residues abolishes the enzymatic activity but preserves the mitogenic properties of the protein. In contrast, inhibitor binding promotes the closure of the interdomain crevice and completely abrogates B cell proliferation, suggesting that the mitogenic properties of TcPRACA depend on the exposure of transient epitopes in the ligand-free enzyme.
Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma cruzi proline racemase.,Buschiazzo A, Goytia M, Schaeffer F, Degrave W, Shepard W, Gregoire C, Chamond N, Cosson A, Berneman A, Coatnoan N, Alzari PM, Minoprio P Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1705-10. Epub 2006 Jan 30. PMID:16446443[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Reina-San-Martin B, Degrave W, Rougeot C, Cosson A, Chamond N, Cordeiro-Da-Silva A, Arala-Chaves M, Coutinho A, Minoprio P. A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase. Nat Med. 2000 Aug;6(8):890-7. PMID:10932226 doi:http://dx.doi.org/10.1038/78651
- ↑ Chamond N, Goytia M, Coatnoan N, Barale JC, Cosson A, Degrave WM, Minoprio P. Trypanosoma cruzi proline racemases are involved in parasite differentiation and infectivity. Mol Microbiol. 2005 Oct;58(1):46-60. PMID:16164548 doi:http://dx.doi.org/MMI4808
- ↑ Buschiazzo A, Goytia M, Schaeffer F, Degrave W, Shepard W, Gregoire C, Chamond N, Cosson A, Berneman A, Coatnoan N, Alzari PM, Minoprio P. Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma cruzi proline racemase. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1705-10. Epub 2006 Jan 30. PMID:16446443
- ↑ Buschiazzo A, Goytia M, Schaeffer F, Degrave W, Shepard W, Gregoire C, Chamond N, Cosson A, Berneman A, Coatnoan N, Alzari PM, Minoprio P. Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma cruzi proline racemase. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1705-10. Epub 2006 Jan 30. PMID:16446443
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