5e2q
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of human DPP3 in complex with angiotensin-II== | |
| + | <StructureSection load='5e2q' size='340' side='right' caption='[[5e2q]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5e2q]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E2Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E2Q 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></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=5e2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e2q OCA], [http://pdbe.org/5e2q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e2q RCSB], [http://www.ebi.ac.uk/pdbsum/5e2q PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM:[http://omim.org/entry/145500 145500]]. Essential hypertension is a condition in which blood pressure is consistently higher than normal with no identifiable cause. Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:[http://omim.org/entry/267430 267430]]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/DPP3_HUMAN DPP3_HUMAN]] Cleaves Arg-Arg-beta-naphthylamide. [[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-3: stimulates aldosterone release.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> | ||
| + | <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> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5e2q" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Dipeptidyl-peptidase III]] | ||
[[Category: Gruber, K]] | [[Category: Gruber, K]] | ||
| - | [[Category: | + | [[Category: Kumar, P]] |
[[Category: Reisinger, M]] | [[Category: Reisinger, M]] | ||
| + | [[Category: Reithofer, V]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Peptidase]] | ||
| + | [[Category: Zinc-hydrolase]] | ||
Revision as of 11:25, 12 May 2016
Structure of human DPP3 in complex with angiotensin-II
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