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| | <StructureSection load='2eep' size='340' side='right'caption='[[2eep]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2eep' size='340' side='right'caption='[[2eep]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2eep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Porgi Porgi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EEP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2eep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Porphyromonas_gingivalis_W83 Porphyromonas gingivalis W83]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EEP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AIO:[(2R)-1-(L-ALANYL-L-ISOLEUCYL)PYRROLIDIN-2-YL]BORONIC+ACID'>AIO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2d5l|2d5l]], [[2dcm|2dcm]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AIO:[(2R)-1-(L-ALANYL-L-ISOLEUCYL)PYRROLIDIN-2-YL]BORONIC+ACID'>AIO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PG1361 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=242619 PORGI])</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=2eep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eep OCA], [https://pdbe.org/2eep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2eep RCSB], [https://www.ebi.ac.uk/pdbsum/2eep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2eep ProSAT]</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=2eep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eep OCA], [https://pdbe.org/2eep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2eep RCSB], [https://www.ebi.ac.uk/pdbsum/2eep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2eep ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PTP_PORGI PTP_PORGI]] Serine proteinase. Releases tripeptides from the free amino terminus of proteins. Has a requirement for Pro in the P1 position, but is inactivated by Pro in the P1' position.<ref>PMID:10092598</ref>
| + | [https://www.uniprot.org/uniprot/PTP_PORGI PTP_PORGI] Serine proteinase. Releases tripeptides from the free amino terminus of proteins. Has a requirement for Pro in the P1 position, but is inactivated by Pro in the P1' position.<ref>PMID:10092598</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Porgi]] | + | [[Category: Porphyromonas gingivalis W83]] |
| - | [[Category: Ito, K]] | + | [[Category: Ito K]] |
| - | [[Category: Nakajima, Y]] | + | [[Category: Nakajima Y]] |
| - | [[Category: Xu, Y]] | + | [[Category: Xu Y]] |
| - | [[Category: Yoshimoto, T]] | + | [[Category: Yoshimoto T]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor complex]]
| + | |
| - | [[Category: Peptidase family s9]]
| + | |
| - | [[Category: Prolyl oligopeptidase family]]
| + | |
| - | [[Category: Serine peptidase]]
| + | |
| Structural highlights
Function
PTP_PORGI Serine proteinase. Releases tripeptides from the free amino terminus of proteins. Has a requirement for Pro in the P1 position, but is inactivated by Pro in the P1' position.[1]
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
A new inhibitor, H-Ala-Ile-pyrrolidin-2-yl boronic acid, was developed as an inhibitor against prolyl tripeptidyl aminopeptidase with a K(i) value of 88.1 nM. The structure of the prolyl tripeptidyl aminopeptidase complexed with the inhibitor (enzyme-inhibitor complex) was determined at 2.2 A resolution. The inhibitor was bound to the active site through a covalent bond between Ser603 and the boron atom of the inhibitor. This structure should closely mimic the structure of the reaction intermediate between the enzyme and substrate. We previously proposed that two glutamate residues, Glu205 and Glu636, are involved in the recognition of substrates. In order to clarify the function of these glutamate residues in substrate recognition, three mutant enzymes, E205A, E205Q, and E636A were generated by site-directed mutagenesis. The E205A mutant was expressed as an inclusion body. The E205Q mutant was expressed in soluble form, but no activity was detected. Here, the structures of the E636A mutant and its complex with the inhibitor were determined. The inhibitor was located at almost the same position as in the wild-type enzyme-inhibitor complex. The amino group of the inhibitor interacted with Glu205 and the main-chain carbonyl group of Gln203. In addition, a water molecule in the place of Glu636 of the wild-type enzyme interacted with the amino group of the inhibitor. This water molecule was located near the position of Glu636 in the wild-type and formed a hydrogen bond with Gln203. The k(cat)/K(M) values of the E636A mutant toward the two substrates used were smaller than those of the wild-type by two orders of magnitude. The K(i) value of our inhibitor for the E636A mutant was 48.8 microM, which was 554-fold higher than that against the wild-type enzyme. Consequently, it was concluded that Glu205 and Glu636 are significant residues for the N-terminal recognition of a substrate.
Novel inhibitor for prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis and details of substrate-recognition mechanism.,Xu Y, Nakajima Y, Ito K, Zheng H, Oyama H, Heiser U, Hoffmann T, Gartner UT, Demuth HU, Yoshimoto T J Mol Biol. 2008 Jan 18;375(3):708-19. Epub 2007 Oct 3. PMID:18042490[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Banbula A, Mak P, Bugno M, Silberring J, Dubin A, Nelson D, Travis J, Potempa J. Prolyl tripeptidyl peptidase from Porphyromonas gingivalis. A novel enzyme with possible pathological implications for the development of periodontitis. J Biol Chem. 1999 Apr 2;274(14):9246-52. PMID:10092598
- ↑ Xu Y, Nakajima Y, Ito K, Zheng H, Oyama H, Heiser U, Hoffmann T, Gartner UT, Demuth HU, Yoshimoto T. Novel inhibitor for prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis and details of substrate-recognition mechanism. J Mol Biol. 2008 Jan 18;375(3):708-19. Epub 2007 Oct 3. PMID:18042490 doi:10.1016/j.jmb.2007.09.077
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