3sfc: Difference between revisions
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==Structure-Based Optimization of Potent 4- and 6-Azaindole-3-Carboxamides as Renin Inhibitors== | |||
<StructureSection load='3sfc' size='340' side='right' caption='[[3sfc]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3sfc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SFC FirstGlance]. <br> | |||
==Disease== | </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=S53:[7-BENZYL-2-(5-FLUORO-2-METHYLPHENOXY)-1-PHENYL-1H-PYRROLO[2,3-C]PYRIDIN-3-YL](PIPERAZIN-1-YL)METHANONE'>S53</scene></td></tr> | ||
[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[http://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> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3oot|3oot]], [[3oqk|3oqk]], [[3oqf|3oqf]]</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=3sfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sfc RCSB], [http://www.ebi.ac.uk/pdbsum/3sfc PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[http://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:[http://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 == | |||
[[http://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 == | |||
The control of hypertension and associated cardiovascular risk factors is possible by selective inhibition of the aspartyl protease renin due to its unique position in the renin-angiotensin system. Starting from a previously disclosed series of potent and nonchiral indole-3-carboxamides, we further explored this motif by structure-based drug design guided by X-ray crystallography in combination with efficient parallel synthesis. This resulted in the discovery of 4- or 6-azaindole derivatives with remarkable potency for renin inhibition. The best compound from these series showed an IC(50) value of 1.3nM. | |||
Structure-based optimization of potent 4- and 6-azaindole-3-carboxamides as renin inhibitors.,Scheiper B, Matter H, Steinhagen H, Bocskei Z, Fleury V, McCort G Bioorg Med Chem Lett. 2011 Sep 15;21(18):5480-6. Epub 2011 Jul 6. PMID:21840218<ref>PMID:21840218</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Renin|Renin]] | *[[Renin|Renin]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Renin]] | [[Category: Renin]] | ||
[[Category: Bocskei, Z | [[Category: Bocskei, Z]] | ||
[[Category: Fleury, V | [[Category: Fleury, V]] | ||
[[Category: Matter, H | [[Category: Matter, H]] | ||
[[Category: McCort, G | [[Category: McCort, G]] | ||
[[Category: Scheiper, B | [[Category: Scheiper, B]] | ||
[[Category: Steinhagen, H]] | [[Category: Steinhagen, H]] | ||
[[Category: Aspartyl protease]] | [[Category: Aspartyl protease]] | ||
