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| | ==Structure of DPP2== | | ==Structure of DPP2== |
| - | <StructureSection load='4ebb' size='340' side='right' caption='[[4ebb]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4ebb' size='340' side='right'caption='[[4ebb]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ebb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EBB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ebb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EBB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ebb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ebb OCA], [https://pdbe.org/4ebb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ebb RCSB], [https://www.ebi.ac.uk/pdbsum/4ebb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ebb ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jyh|3jyh]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DPP7, DPP2, QPP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_II Dipeptidyl-peptidase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.2 3.4.14.2] </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=4ebb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ebb OCA], [http://pdbe.org/4ebb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ebb RCSB], [http://www.ebi.ac.uk/pdbsum/4ebb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ebb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DPP2_HUMAN DPP2_HUMAN]] Plays an important role in the degradation of some oligopeptides.<ref>PMID:15487984</ref> | + | [[https://www.uniprot.org/uniprot/DPP2_HUMAN DPP2_HUMAN]] Plays an important role in the degradation of some oligopeptides.<ref>PMID:15487984</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Dipeptidyl peptidase|Dipeptidyl peptidase]] | + | *[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dipeptidyl-peptidase II]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Hassell, A H]] | + | [[Category: Hassell AH]] |
| - | [[Category: Johanson, K O]] | + | [[Category: Johanson KO]] |
| - | [[Category: Kennedy-Wilson, K M]] | + | [[Category: Kennedy-Wilson KM]] |
| - | [[Category: McDevitt, P J]] | + | [[Category: McDevitt PJ]] |
| - | [[Category: Shewchuk, L M]] | + | [[Category: Shewchuk LM]] |
| - | [[Category: Sweitzer, S M]] | + | [[Category: Sweitzer SM]] |
| - | [[Category: Sweitzer, T D]] | + | [[Category: Sweitzer TD]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Peptidase]]
| + | |
| Structural highlights
Function
[DPP2_HUMAN] Plays an important role in the degradation of some oligopeptides.[1]
Publication Abstract from PubMed
Proline-specific dipeptidyl peptidases (DPPs) are emerging targets for drug development. DPP4 inhibitors are approved in many countries, and other dipeptidyl peptidases are often referred to as DPP4 activity- and/or structure-homologues (DASH). Members of the DASH family have overlapping substrate specificities, and, even though they share low sequence identity, therapeutic or clinical cross-reactivity is a concern. Here, we report the structure of human DPP7 and its complex with a selective inhibitor Dab-Pip (L-2,4-diaminobutyryl-piperidinamide) and compare it with that of DPP4. Both enzymes share a common catalytic domain (alpha/beta-hydrolase). The catalytic pocket is located in the interior of DPP7, deep inside the cleft between the two domains. Substrates might access the active site via a narrow tunnel. The DPP7 catalytic triad is completely conserved and comprises Ser162, Asp418 and His443 (corresponding to Ser630, Asp708 and His740 in DPP4), while other residues lining the catalytic pockets differ considerably. The "specificity domains" are structurally also completely different exhibiting a beta-propeller fold in DPP4 compared to a rare, completely helical fold in DPP7. Comparing the structures of DPP7 and DPP4 allows the design of specific inhibitors and thus the development of less cross-reactive drugs. Furthermore, the reported DPP7 structures shed some light onto the evolutionary relationship of prolyl-specific peptidases through the analysis of the architectural organization of their domains.
Structures of Human DPP7 Reveal the Molecular Basis of Specific Inhibition and the Architectural Diversity of Proline-Specific Peptidases.,Bezerra GA, Dobrovetsky E, Dong A, Seitova A, Crombett L, Shewchuk LM, Hassell AM, Sweitzer SM, Sweitzer TD, McDevitt PJ, Johanson KO, Kennedy-Wilson KM, Cossar D, Bochkarev A, Gruber K, Dhe-Paganon S PLoS One. 2012;7(8):e43019. Epub 2012 Aug 29. PMID:22952628[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Maes MB, Lambeir AM, Gilany K, Senten K, Van der Veken P, Leiting B, Augustyns K, Scharpe S, De Meester I. Kinetic investigation of human dipeptidyl peptidase II (DPPII)-mediated hydrolysis of dipeptide derivatives and its identification as quiescent cell proline dipeptidase (QPP)/dipeptidyl peptidase 7 (DPP7). Biochem J. 2005 Mar 1;386(Pt 2):315-24. PMID:15487984 doi:http://dx.doi.org/10.1042/BJ20041156
- ↑ Bezerra GA, Dobrovetsky E, Dong A, Seitova A, Crombett L, Shewchuk LM, Hassell AM, Sweitzer SM, Sweitzer TD, McDevitt PJ, Johanson KO, Kennedy-Wilson KM, Cossar D, Bochkarev A, Gruber K, Dhe-Paganon S. Structures of Human DPP7 Reveal the Molecular Basis of Specific Inhibition and the Architectural Diversity of Proline-Specific Peptidases. PLoS One. 2012;7(8):e43019. Epub 2012 Aug 29. PMID:22952628 doi:http://dx.doi.org/10.1371/journal.pone.0043019
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