This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4xx3

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Renin in complex with (S)-1-(3-(benzylcarbamoyl)benzyl)-4-isopropyl-4-methyl-6-oxotetrahydropyrimidin-2(1H)-iminium

Structural highlights

4xx3 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.
Method:	X-ray diffraction, Resolution 2.4Å
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

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/4xx3"

Categories: Homo sapiens | Large Structures | Orth P

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4xx3]] 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=4XX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XX3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=70X:N-BENZYL-3-{[(2Z,4S)-2-IMINO-4-METHYL-6-OXO-4-(PROPAN-2-YL)TETRAHYDROPYRIMIDIN-1(2H)-YL]METHYL}BENZAMIDE'>70X</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=70X:N-BENZYL-3-{[(2Z,4S)-2-IMINO-4-METHYL-6-OXO-4-(PROPAN-2-YL)TETRAHYDROPYRIMIDIN-1(2H)-YL]METHYL}BENZAMIDE'>70X</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4xx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx3 OCA], [https://pdbe.org/4xx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xx3 RCSB], [https://www.ebi.ac.uk/pdbsum/4xx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xx3 ProSAT]</span></td></tr>
 </table>

4xx3

From Proteopedia

Current revision

Renin in complex with (S)-1-(3-(benzylcarbamoyl)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?)

Views

Personal tools

Navigation

Search

Toolbox