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4s1g

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Revision as of 01:09, 19 January 2017

Rein in complex with (S)-1-(3-fluoro-5-(((S)-1-phenylethyl)carbamoyl)benzyl)-4-isopropyl-4-methyl-6-oxotetrahydropyrimidin-2(1H)-iminium

Structural highlights

4s1g is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
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

The development of renin inhibitors with favorable oral pharmacokinetic profiles has been a longstanding challenge for the pharmaceutical industry. As part of our work to identify inhibitors of BACE1, we have previously developed iminopyrimidinones as a novel pharmacophore for aspartyl protease inhibition. In this letter we describe how we modified substitution around this pharmacophore to develop a potent, selective and orally active renin inhibitor.

Iminopyrimidinones: A novel pharmacophore for the development of orally active renin inhibitors.,McKittrick BA, Caldwell JP, Bara T, Boykow G, Chintala M, Clader J, Czarniecki M, Courneya B, Duffy R, Fleming L, Giessert R, Greenlee WJ, Heap C, Hong L, Huang Y, Iserloh U, Josien H, Khan T, Korfmacher W, Liang X, Mazzola R, Mitra S, Moore K, Orth P, Rajagopalan M, Roy S, Sakwa S, Strickland C, Vaccaro H, Voigt J, Wang H, Wong J, Zhang R, Zych A Bioorg Med Chem Lett. 2015 Feb 10. pii: S0960-894X(15)00096-7. doi:, 10.1016/j.bmcl.2015.02.003. PMID:25728416^[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
↑ McKittrick BA, Caldwell JP, Bara T, Boykow G, Chintala M, Clader J, Czarniecki M, Courneya B, Duffy R, Fleming L, Giessert R, Greenlee WJ, Heap C, Hong L, Huang Y, Iserloh U, Josien H, Khan T, Korfmacher W, Liang X, Mazzola R, Mitra S, Moore K, Orth P, Rajagopalan M, Roy S, Sakwa S, Strickland C, Vaccaro H, Voigt J, Wang H, Wong J, Zhang R, Zych A. Iminopyrimidinones: A novel pharmacophore for the development of orally active renin inhibitors. Bioorg Med Chem Lett. 2015 Feb 10. pii: S0960-894X(15)00096-7. doi:, 10.1016/j.bmcl.2015.02.003. PMID:25728416 doi:http://dx.doi.org/10.1016/j.bmcl.2015.02.003

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/4s1g"

@@ Line 1: / Line 1: @@
 ==Rein in complex with (S)-1-(3-fluoro-5-(((S)-1-phenylethyl)carbamoyl)benzyl)-4-isopropyl-4-methyl-6-oxotetrahydropyrimidin-2(1H)-iminium==
 <StructureSection load='4s1g' size='340' side='right' caption='[[4s1g]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=43T:3-{[(4S)-2-AMINO-4-METHYL-6-OXO-4-(PROPAN-2-YL)-5,6-DIHYDROPYRIMIDIN-1(4H)-YL]METHYL}-5-FLUORO-N-[(1S)-1-PHENYLETHYL]BENZAMIDE'>43T</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4s1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s1g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4s1g RCSB], [http://www.ebi.ac.uk/pdbsum/4s1g 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=4s1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s1g OCA], [http://pdbe.org/4s1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s1g RCSB], [http://www.ebi.ac.uk/pdbsum/4s1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s1g ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4s1g" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Renin|Renin]]
 == References ==
 <references/>

4s1g

From Proteopedia

Revision as of 01:09, 19 January 2017

Rein in complex with (S)-1-(3-fluoro-5-(((S)-1-phenylethyl)carbamoyl)benzyl)-4-isopropyl-4-methyl-6-oxotetrahydropyrimidin-2(1H)-iminium

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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