View source for 3oqk


==Crystal Structure Analysis of Renin-indole-piperazin inhibitor complexes==
<StructureSection load='3oqk' size='340' side='right'caption='[[3oqk]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3oqk]] 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=3OQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OQK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=S52:2-PHENOXY-1-PHENYL-3-(PIPERAZIN-1-YLCARBONYL)-1H-INDOLE'>S52</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=3oqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oqk OCA], [https://pdbe.org/3oqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oqk RCSB], [https://www.ebi.ac.uk/pdbsum/3oqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oqk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[https://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:[https://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 ==
[https://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 ==
Selective inhibition of the aspartyl protease renin has gained attraction as an interesting approach to control hypertension and associated cardiovascular risk factors given its unique position in the renin-angiotensin system. Using a combination of high-throughput screening, parallel synthesis, X-ray crystallography and structure-based design, we identified and optimized a novel series of potent and non-chiral indole-3-carboxamides with remarkable potency for renin. The most potent compound 5k displays an IC(50) value of 2nM.

Discovery and optimization of a new class of potent and non-chiral indole-3-carboxamide-based renin inhibitors.,Scheiper B, Matter H, Steinhagen H, Stilz U, Bocskei Z, Fleury V, McCort G Bioorg Med Chem Lett. 2010 Nov 1;20(21):6268-72. Epub 2010 Aug 21. PMID:20850300<ref>PMID:20850300</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3oqk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Renin|Renin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bocskei Z]]