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4ryg

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RENIN IN COMPLEXED WITH N-({(3S,4S)-4-[(benzylsulfonyl)amino]pyrrolidin-3-yl}methyl)-4-methoxy-3-(3-methoxypropoxy)-N-(propan-2-yl)benzamide INHIBITOR

Structural highlights

4ryg is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

RENI_HUMAN Defects in REN 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] Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:613092. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.^[2]

Function

RENI_HUMAN Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.

Publication Abstract from PubMed

Recently, we reported on the discovery of (3S,4S)-disubstituted pyrrolidines (e.g., 2) as inhibitors of the human aspartyl protease renin. In our effort to further expand the scope of this novel class of direct renin inhibitors, a new sub-series was designed in which the prime site substituents are linked to the pyrrolidine core by a (3S)-amino functional group. In particular, analogs bearing the corresponding sulfonamide spacer (50, 51 and 54a) demonstrated a pronounced increase in in vitro potency compared to compound 2.

trans-(3S,4S)-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease renin. Part I: Prime site exploration using an amino linker.,Lorthiois E, Cumin F, Ehrhardt C, Kosaka T, Sellner H, Ostermann N, Francotte E, Wagner T, Maibaum J Bioorg Med Chem Lett. 2015 Apr 15;25(8):1782-6. doi: 10.1016/j.bmcl.2015.02.039. , Epub 2015 Feb 21. PMID:25782742^[3]

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
↑ Zivna M, Hulkova H, Matignon M, Hodanova K, Vylet'al P, Kalbacova M, Baresova V, Sikora J, Blazkova H, Zivny J, Ivanek R, Stranecky V, Sovova J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gubler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S. Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet. 2009 Aug;85(2):204-13. Epub 2009 Aug 6. PMID:19664745 doi:10.1016/j.ajhg.2009.07.010
↑ Lorthiois E, Cumin F, Ehrhardt C, Kosaka T, Sellner H, Ostermann N, Francotte E, Wagner T, Maibaum J. trans-(3S,4S)-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease renin. Part I: Prime site exploration using an amino linker. Bioorg Med Chem Lett. 2015 Apr 15;25(8):1782-6. doi: 10.1016/j.bmcl.2015.02.039. , Epub 2015 Feb 21. PMID:25782742 doi:http://dx.doi.org/10.1016/j.bmcl.2015.02.039

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/4ryg"

Categories: Homo sapiens | Large Structures | Ostermann N

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4ryg is ON HOLD
+==RENIN IN COMPLEXED WITH N-({(3S,4S)-4-[(benzylsulfonyl)amino]pyrrolidin-3-yl}methyl)-4-methoxy-3-(3-methoxypropoxy)-N-(propan-2-yl)benzamide INHIBITOR==
+<StructureSection load='4ryg' size='340' side='right'caption='[[4ryg]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ryg]] 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=4RYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RYG FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3ZJ:N-({(3S,4S)-4-[(BENZYLSULFONYL)AMINO]PYRROLIDIN-3-YL}METHYL)-4-METHOXY-3-(3-METHOXYPROPOXY)-N-(PROPAN-2-YL)BENZAMIDE'>3ZJ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4ryg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ryg OCA], [https://pdbe.org/4ryg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ryg RCSB], [https://www.ebi.ac.uk/pdbsum/4ryg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ryg ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[https://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>   Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:[https://omim.org/entry/613092 613092]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.<ref>PMID:19664745</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Recently, we reported on the discovery of (3S,4S)-disubstituted pyrrolidines (e.g., 2) as inhibitors of the human aspartyl protease renin. In our effort to further expand the scope of this novel class of direct renin inhibitors, a new sub-series was designed in which the prime site substituents are linked to the pyrrolidine core by a (3S)-amino functional group. In particular, analogs bearing the corresponding sulfonamide spacer (50, 51 and 54a) demonstrated a pronounced increase in in vitro potency compared to compound 2.
-Authors: Ostermann, Nils
+trans-(3S,4S)-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease renin. Part I: Prime site exploration using an amino linker.,Lorthiois E, Cumin F, Ehrhardt C, Kosaka T, Sellner H, Ostermann N, Francotte E, Wagner T, Maibaum J Bioorg Med Chem Lett. 2015 Apr 15;25(8):1782-6. doi: 10.1016/j.bmcl.2015.02.039. , Epub 2015 Feb 21. PMID:25782742<ref>PMID:25782742</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4ryg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Renin|Renin]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Ostermann N]]

4ryg

From Proteopedia

Current revision

RENIN IN COMPLEXED WITH N-({(3S,4S)-4-[(benzylsulfonyl)amino]pyrrolidin-3-yl}methyl)-4-methoxy-3-(3-methoxypropoxy)-N-(propan-2-yl)benzamide INHIBITOR

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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