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3q3t

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Revision as of 16:16, 4 August 2016

Alkyl Amine Renin Inhibitors: Filling S1 from S3

Structural highlights

3q3t is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3gw5, 3km4, 3q4b, 3q5h
Gene:	REN, renin (HUMAN)
Activity:	Renin, with EC number 3.4.23.15
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

Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension.

Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket.,Yuan J, Simpson RD, Zhao W, Tice CM, Xu Z, Cacatian S, Jia L, Flaherty PT, Guo J, Ishchenko A, Wu Z, McKeever BM, Scott BB, Bukhtiyarov Y, Berbaum J, Panemangalore R, Bentley R, Doe CP, Harrison RK, McGeehan GM, Singh SB, Dillard LW, Baldwin JJ, Claremon DA Bioorg Med Chem Lett. 2011 Aug 15;21(16):4836-43. Epub 2011 Jun 17. PMID:21741239^[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
↑ Yuan J, Simpson RD, Zhao W, Tice CM, Xu Z, Cacatian S, Jia L, Flaherty PT, Guo J, Ishchenko A, Wu Z, McKeever BM, Scott BB, Bukhtiyarov Y, Berbaum J, Panemangalore R, Bentley R, Doe CP, Harrison RK, McGeehan GM, Singh SB, Dillard LW, Baldwin JJ, Claremon DA. Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4836-43. Epub 2011 Jun 17. PMID:21741239 doi:10.1016/j.bmcl.2011.06.043

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/3q3t"

@@ Line 1: / Line 1: @@
 ==Alkyl Amine Renin Inhibitors: Filling S1 from S3==
 <StructureSection load='3q3t' size='340' side='right' caption='[[3q3t]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3q3t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q3T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q3T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3q3t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q3T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q3T FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RX0:[(1S,3R,4S)-3-AMINO-4-HYDROXYCYCLOPENTYL]{(3R)-3-[(1S)-1-(BIPHENYL-2-YL)-1-HYDROXY-5-METHOXYPENTYL]PIPERIDIN-1-YL}METHANONE'>RX0</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gw5|3gw5]], [[3km4|3km4]], [[3q4b|3q4b]], [[3q5h|3q5h]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">REN, renin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">REN, renin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Renin Renin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.15 3.4.23.15] </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=3q3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q3t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q3t RCSB], [http://www.ebi.ac.uk/pdbsum/3q3t PDBsum]</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=3q3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q3t OCA], [http://pdbe.org/3q3t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3q3t RCSB], [http://www.ebi.ac.uk/pdbsum/3q3t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3q3t ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3q3t" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 28: / Line 30: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Renin]]
 [[Category: McKeever, B]]

3q3t

From Proteopedia

Revision as of 16:16, 4 August 2016

Alkyl Amine Renin Inhibitors: Filling S1 from S3

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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