5ehh: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='5ehh' size='340' side='right'caption='[[5ehh]], [[Resolution|resolution]] 2.38Å' scene=''> | <StructureSection load='5ehh' size='340' side='right'caption='[[5ehh]], [[Resolution|resolution]] 2.38Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ehh]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EHH OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5ehh]] 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=5EHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EHH FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38Å</td></tr> | ||
<tr id=' | <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=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5ehh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ehh OCA], [https://pdbe.org/5ehh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ehh RCSB], [https://www.ebi.ac.uk/pdbsum/5ehh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ehh ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DPP3_HUMAN DPP3_HUMAN] Cleaves Arg-Arg-beta-naphthylamide. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 28: | Line 26: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gruber | [[Category: Gruber K]] | ||
[[Category: Kumar | [[Category: Kumar P]] | ||
[[Category: Macheroux | [[Category: Macheroux P]] | ||
[[Category: Pavkov-Keller | [[Category: Pavkov-Keller T]] | ||
[[Category: Reisinger | [[Category: Reisinger M]] | ||
[[Category: Reithofer | [[Category: Reithofer V]] | ||
[[Category: Wallner | [[Category: Wallner S]] | ||
Latest revision as of 09:28, 5 July 2023
Structure of human DPP3 in complex with endomorphin-2.Structure of human DPP3 in complex with endomorphin-2.
Structural highlights
FunctionDPP3_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
|
| ||||||||||||||||||