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3gw5

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Revision as of 07:15, 1 November 2017

Crystal structure of human renin complexed with a novel inhibitor

Structural highlights

3gw5 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:	, , ,
Gene:	REN (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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Structure-based drug design led to the identification of a novel class of potent, low MW alkylamine renin inhibitors. Oral administration of lead compound 21l, with MW of 508 and IC(50) of 0.47nM, caused a sustained reduction in mean arterial blood pressure in a double transgenic rat model of hypertension.

Design and optimization of renin inhibitors: Orally bioavailable alkyl amines.,Tice CM, Xu Z, Yuan J, Simpson RD, Cacatian ST, Flaherty PT, Zhao W, Guo J, Ishchenko A, Singh SB, Wu Z, Scott BB, Bukhtiyarov Y, Berbaum J, Mason J, Panemangalore R, Cappiello MG, Muller D, Harrison RK, McGeehan GM, Dillard LW, Baldwin JJ, Claremon DA Bioorg Med Chem Lett. 2009 Jul 1;19(13):3541-5. Epub 2009 May 5. PMID:19457666^[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
↑ Tice CM, Xu Z, Yuan J, Simpson RD, Cacatian ST, Flaherty PT, Zhao W, Guo J, Ishchenko A, Singh SB, Wu Z, Scott BB, Bukhtiyarov Y, Berbaum J, Mason J, Panemangalore R, Cappiello MG, Muller D, Harrison RK, McGeehan GM, Dillard LW, Baldwin JJ, Claremon DA. Design and optimization of renin inhibitors: Orally bioavailable alkyl amines. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3541-5. Epub 2009 May 5. PMID:19457666 doi:10.1016/j.bmcl.2009.04.140

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3gw5"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human renin complexed with a novel inhibitor==
 <StructureSection load='3gw5' size='340' side='right' caption='[[3gw5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">REN ([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=3gw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gw5 OCA], [http://pdbe.org/3gw5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gw5 RCSB], [http://www.ebi.ac.uk/pdbsum/3gw5 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=3gw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gw5 OCA], [http://pdbe.org/3gw5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gw5 RCSB], [http://www.ebi.ac.uk/pdbsum/3gw5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gw5 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 3gw5" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Renin|Renin]]
 == References ==
 <references/>

3gw5

From Proteopedia

Revision as of 07:15, 1 November 2017

Crystal structure of human renin complexed with a novel inhibitor

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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