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| | ==Oligopeptidase B from Trypanosoma brucei - open form== | | ==Oligopeptidase B from Trypanosoma brucei - open form== |
| - | <StructureSection load='4bp8' size='340' side='right' caption='[[4bp8]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4bp8' size='340' side='right'caption='[[4bp8]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bp8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BP8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BP8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bp8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BP8 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bp9|4bp9]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Oligopeptidase_B Oligopeptidase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.83 3.4.21.83] </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=4bp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bp8 OCA], [https://pdbe.org/4bp8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bp8 RCSB], [https://www.ebi.ac.uk/pdbsum/4bp8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bp8 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=4bp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bp8 OCA], [http://pdbe.org/4bp8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bp8 RCSB], [http://www.ebi.ac.uk/pdbsum/4bp8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bp8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/O76728_TRYBB O76728_TRYBB] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Oligopeptidase B]] | + | [[Category: Large Structures]] |
| - | [[Category: Canning, P]] | + | [[Category: Trypanosoma brucei]] |
| - | [[Category: Fulop, V]] | + | [[Category: Canning P]] |
| - | [[Category: Morty, R]] | + | [[Category: Fulop V]] |
| - | [[Category: Rea, D]] | + | [[Category: Morty R]] |
| - | [[Category: Catalytic regulation]]
| + | [[Category: Rea D]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Induced fit]]
| + | |
| - | [[Category: Prolyl oligopeptidase]]
| + | |
| Structural highlights
Function
O76728_TRYBB
Publication Abstract from PubMed
Oligopeptidase B cleaves after basic amino acids in peptides up to 30 residues. As a virulence factor in bacteria and trypanosomatid pathogens that is absent in higher eukaryotes, this is a promising drug target. Here we present ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness. These (and related) structures show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Peptides over 30 residues cannot fit the enzyme cavity, preventing the complete domain closure required for a key propeller Asp/Glu to fix the catalytic His and Arg in the catalytically competent conformation. This size exclusion mechanism protects larger peptides and proteins from degradation. Similar bacterial prolyl endopeptidase and archael acylaminoacyl peptidase structures demonstrate this mechanism is conserved among oligopeptidase family enzymes across all three domains of life.
Crystal structures of Trypanosoma brucei oligopeptidase B broaden the paradigm of catalytic regulation in prolyl oligopeptidase family enzymes.,Canning P, Rea D, Morty RE, Fulop V PLoS One. 2013 Nov 12;8(11):e79349. doi: 10.1371/journal.pone.0079349., eCollection 2013. PMID:24265767[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Canning P, Rea D, Morty RE, Fulop V. Crystal structures of Trypanosoma brucei oligopeptidase B broaden the paradigm of catalytic regulation in prolyl oligopeptidase family enzymes. PLoS One. 2013 Nov 12;8(11):e79349. doi: 10.1371/journal.pone.0079349., eCollection 2013. PMID:24265767 doi:http://dx.doi.org/10.1371/journal.pone.0079349
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