5e3c: Difference between revisions
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==Structure of human DPP3 in complex with hemorphin like opioid peptide IVYPW== | |||
<StructureSection load='5e3c' size='340' side='right' caption='[[5e3c]], [[Resolution|resolution]] 2.77Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5e3c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E3C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E3C FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fvy|3fvy]], [[3t6b|3t6b]]</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_III Dipeptidyl-peptidase III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.4 3.4.14.4] </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=5e3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e3c OCA], [http://pdbe.org/5e3c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e3c RCSB], [http://www.ebi.ac.uk/pdbsum/5e3c PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/DPP3_HUMAN DPP3_HUMAN]] Cleaves Arg-Arg-beta-naphthylamide. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human dipeptidyl-peptidase III (hDPP III) is a zinc-dependent hydrolase cleaving dipeptides off the N-termini of various bioactive peptides. Thus, the enzyme is likely involved in a number of physiological processes such as nociception and is also implicated in several forms of cancer. We present high-resolution crystal structures of hDPP III in complex with opioid peptides (Met-and Leu-enkephalin, endomorphin-2) as well as with angiotensin-II and the peptide inhibitor IVYPW. These structures confirm the previously reported large conformational change of the enzyme upon ligand binding and show that the structure of the closed conformation is independent of the nature of the bound peptide. The overall peptide-binding mode is also conserved ensuring the correct positioning of the scissile peptide bond with respect to the catalytic zinc ion. The structure of the angiotensin-II complex shows, how longer peptides are accommodated in the binding cleft of hDPP III. Differences in the binding modes allow a distinction between real substrates and inhibitory peptides or "slow" substrates. The latter displace a zinc bound water molecule necessitating the energetically much less favoured anhydride mechanism as opposed to the favoured promoted-water mechanism. The structural data also form the necessary framework for the design of specific hDPP III inhibitors. | |||
Substrate complexes of human dipeptidyl peptidase III reveal the mechanism of enzyme inhibition.,Kumar P, Reithofer V, Reisinger M, Wallner S, Pavkov-Keller T, Macheroux P, Gruber K Sci Rep. 2016 Mar 30;6:23787. doi: 10.1038/srep23787. PMID:27025154<ref>PMID:27025154</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5e3c" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dipeptidyl-peptidase III]] | |||
[[Category: Gruber, K]] | |||
[[Category: Kumar, P]] | [[Category: Kumar, P]] | ||
[[Category: Macheroux, P]] | |||
[[Category: Pavkov-Keller, T]] | [[Category: Pavkov-Keller, T]] | ||
[[Category: Reisinger, M]] | [[Category: Reisinger, M]] | ||
[[Category: Reithofer, V]] | [[Category: Reithofer, V]] | ||
[[Category: | [[Category: Wallner, S]] | ||
[[Category: Hydrolase]] | |||
[[Category: Inhibitor complex]] | |||
[[Category: Opioid-peptide]] | |||
[[Category: Peptidase]] | |||
[[Category: Zinc-hydrolase]] | |||
Revision as of 14:25, 12 May 2016
Structure of human DPP3 in complex with hemorphin like opioid peptide IVYPWStructure of human DPP3 in complex with hemorphin like opioid peptide IVYPW
Structural highlights
Function[DPP3_HUMAN] Cleaves Arg-Arg-beta-naphthylamide. Publication Abstract from PubMedHuman dipeptidyl-peptidase III (hDPP III) is a zinc-dependent hydrolase cleaving dipeptides off the N-termini of various bioactive peptides. Thus, the enzyme is likely involved in a number of physiological processes such as nociception and is also implicated in several forms of cancer. We present high-resolution crystal structures of hDPP III in complex with opioid peptides (Met-and Leu-enkephalin, endomorphin-2) as well as with angiotensin-II and the peptide inhibitor IVYPW. These structures confirm the previously reported large conformational change of the enzyme upon ligand binding and show that the structure of the closed conformation is independent of the nature of the bound peptide. The overall peptide-binding mode is also conserved ensuring the correct positioning of the scissile peptide bond with respect to the catalytic zinc ion. The structure of the angiotensin-II complex shows, how longer peptides are accommodated in the binding cleft of hDPP III. Differences in the binding modes allow a distinction between real substrates and inhibitory peptides or "slow" substrates. The latter displace a zinc bound water molecule necessitating the energetically much less favoured anhydride mechanism as opposed to the favoured promoted-water mechanism. The structural data also form the necessary framework for the design of specific hDPP III inhibitors. Substrate complexes of human dipeptidyl peptidase III reveal the mechanism of enzyme inhibition.,Kumar P, Reithofer V, Reisinger M, Wallner S, Pavkov-Keller T, Macheroux P, Gruber K Sci Rep. 2016 Mar 30;6:23787. doi: 10.1038/srep23787. PMID:27025154[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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