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5e2q

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Revision as of 06:41, 22 April 2020

Structure of human DPP3 in complex with angiotensin-II

Structural highlights

5e2q is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3fvy, 3t6b
Activity:	Dipeptidyl-peptidase III, with EC number 3.4.14.4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ANGT_HUMAN] Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM: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: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).^[1]

Function

[DPP3_HUMAN] Cleaves Arg-Arg-beta-naphthylamide. [ANGT_HUMAN] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.^[2] ^[3] ^[4] 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.^[5] ^[6] ^[7] Angiotensin-3: stimulates aldosterone release.^[8] ^[9] ^[10] 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).^[11] ^[12] ^[13]

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^[14]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005 Sep;37(9):964-8. Epub 2005 Aug 14. PMID:16116425 doi:ng1623
↑ Goodfriend TL, Peach MJ. Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Circ Res. 1975 Jun;36(6 Suppl 1):38-48. PMID:1132082
↑ Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999 Dec;12(12 Pt 3):205S-213S. PMID:10619573
↑ Jankowski V, Vanholder R, van der Giet M, Tolle M, Karadogan S, Gobom J, Furkert J, Oksche A, Krause E, Tran TN, Tepel M, Schuchardt M, Schluter H, Wiedon A, Beyermann M, Bader M, Todiras M, Zidek W, Jankowski J. Mass-spectrometric identification of a novel angiotensin peptide in human plasma. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):297-302. Epub 2006 Nov 30. PMID:17138938 doi:10.1161/01.ATV.0000253889.09765.5f
↑ Goodfriend TL, Peach MJ. Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Circ Res. 1975 Jun;36(6 Suppl 1):38-48. PMID:1132082
↑ Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999 Dec;12(12 Pt 3):205S-213S. PMID:10619573
↑ Jankowski V, Vanholder R, van der Giet M, Tolle M, Karadogan S, Gobom J, Furkert J, Oksche A, Krause E, Tran TN, Tepel M, Schuchardt M, Schluter H, Wiedon A, Beyermann M, Bader M, Todiras M, Zidek W, Jankowski J. Mass-spectrometric identification of a novel angiotensin peptide in human plasma. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):297-302. Epub 2006 Nov 30. PMID:17138938 doi:10.1161/01.ATV.0000253889.09765.5f
↑ Goodfriend TL, Peach MJ. Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Circ Res. 1975 Jun;36(6 Suppl 1):38-48. PMID:1132082
↑ Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999 Dec;12(12 Pt 3):205S-213S. PMID:10619573
↑ Jankowski V, Vanholder R, van der Giet M, Tolle M, Karadogan S, Gobom J, Furkert J, Oksche A, Krause E, Tran TN, Tepel M, Schuchardt M, Schluter H, Wiedon A, Beyermann M, Bader M, Todiras M, Zidek W, Jankowski J. Mass-spectrometric identification of a novel angiotensin peptide in human plasma. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):297-302. Epub 2006 Nov 30. PMID:17138938 doi:10.1161/01.ATV.0000253889.09765.5f
↑ Goodfriend TL, Peach MJ. Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Circ Res. 1975 Jun;36(6 Suppl 1):38-48. PMID:1132082
↑ Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999 Dec;12(12 Pt 3):205S-213S. PMID:10619573
↑ Jankowski V, Vanholder R, van der Giet M, Tolle M, Karadogan S, Gobom J, Furkert J, Oksche A, Krause E, Tran TN, Tepel M, Schuchardt M, Schluter H, Wiedon A, Beyermann M, Bader M, Todiras M, Zidek W, Jankowski J. Mass-spectrometric identification of a novel angiotensin peptide in human plasma. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):297-302. Epub 2006 Nov 30. PMID:17138938 doi:10.1161/01.ATV.0000253889.09765.5f
↑ Kumar P, Reithofer V, Reisinger M, Wallner S, Pavkov-Keller T, Macheroux P, Gruber K. Substrate complexes of human dipeptidyl peptidase III reveal the mechanism of enzyme inhibition. Sci Rep. 2016 Mar 30;6:23787. doi: 10.1038/srep23787. PMID:27025154 doi:http://dx.doi.org/10.1038/srep23787

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e2q"

@@ Line 1: / Line 1: @@
 ==Structure of human DPP3 in complex with angiotensin-II==
-<StructureSection load='5e2q' size='340' side='right' caption='[[5e2q]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5e2q' size='340' side='right'caption='[[5e2q]], [[Resolution|resolution]] 2.40&Aring;' 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>
+<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://proteopedia.org/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>
+</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></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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e2q ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e2q ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 24: / Line 24: @@
 ==See Also==
-*[[Dipeptidyl peptidase|Dipeptidyl peptidase]]
+*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
+*[[Serpin 3D structures|Serpin 3D structures]]
 == References ==
 <references/>
@@ Line 30: / Line 31: @@
 </StructureSection>
 [[Category: Dipeptidyl-peptidase III]]
+[[Category: Large Structures]]
 [[Category: Gruber, K]]
 [[Category: Kumar, P]]

5e2q

From Proteopedia

Revision as of 06:41, 22 April 2020

Structure of human DPP3 in complex with angiotensin-II

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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