5e3c: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Structure of human DPP3 in complex with hemorphin like opioid peptide IVYPW== | ==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=''> | <StructureSection load='5e3c' size='340' side='right'caption='[[5e3c]], [[Resolution|resolution]] 2.77Å' scene=''> | ||
== Structural highlights == | == 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:// | <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://proteopedia.org/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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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='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:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e3c ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 22: | Line 22: | ||
==See Also== | ==See Also== | ||
*[[Dipeptidyl peptidase|Dipeptidyl peptidase]] | *[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 28: | Line 28: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Dipeptidyl-peptidase III]] | [[Category: Dipeptidyl-peptidase III]] | ||
[[Category: Large Structures]] | |||
[[Category: Gruber, K]] | [[Category: Gruber, K]] | ||
[[Category: Kumar, P]] | [[Category: Kumar, P]] | ||
Revision as of 09:42, 22 April 2020
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. See AlsoReferences
|
| ||||||||||||||||||||