4gja - Revision history

OCA at 15:48, 14 March 2024

OCA — Thu, 14 Mar 2024 15:48:33 GMT

←Older revision		Revision as of 15:48, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4gja]] 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=4GJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GJA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4gja]] 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=4GJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GJA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0M3:(3S,5R)-N-(2,2-DIPHENYLETHYL)-5-{[(4-METHYLPHENYL)SULFONYL]AMINO}PIPERIDINE-3-CARBOXAMIDE'>0M3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0M3:(3S,5R)-N-(2,2-DIPHENYLETHYL)-5-{[(4-METHYLPHENYL)SULFONYL]AMINO}PIPERIDINE-3-CARBOXAMIDE'>0M3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4gja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gja OCA], [https://pdbe.org/4gja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gja RCSB], [https://www.ebi.ac.uk/pdbsum/4gja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gja ProSAT]</span></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=4gja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gja OCA], [https://pdbe.org/4gja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gja RCSB], [https://www.ebi.ac.uk/pdbsum/4gja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gja ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== 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.		[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 ==
-	A small library of fragments comprising putative recognition motifs for the catalytic dyad of aspartic proteases was generated by in silico similarity searches within the corporate compound deck based on rh-renin active site docking and scoring filters. Subsequent screening by NMR identified the low-affinity hits 3 and 4 as competitive active site binders, which could be shown by X-ray crystallography to bind to the hydrophobic S3-S1 pocket of rh-renin. As part of a parallel multiple hit-finding approach, the 3,5-disubstituted piperidine (rac)-5 was discovered by HTS using a enzymatic assay. X-ray crystallography demonstrated the eutomer (3S,5R)-5 to be a peptidomimetic inhibitor binding to a nonsubstrate topography of the rh-renin prime site. The design of the potent and selective (3S,5R)-12 bearing a P3sp-tethered tricyclic P3-P1 pharmacophore derived from 3 is described. (3S,5R)-12 showed oral bioavailability in rats and demonstrated blood pressure lowering activity in the double-transgenic rat model.
-
-	A Novel Class of Oral Direct Renin Inhibitors: Highly Potent 3,5-Disubstituted Piperidines bearing a Tricyclic P3-P1 Pharmacophore.,Ostermann N, Ruedisser S, Ehrhardt C, Breitenstein W, Marzinzik AL, Jacoby E, Vangrevelinghe E, Ottl J, Klumpp M, Hartwieg C, Cumin F, Hassiepen U, Trappe J, Sedrani RC, Geisse S, Gerhartz B, Richert P, Francotte E, Wagner T, Kromer M, Kosaka T, Webb RL, Rigel DF, Maibaum JK, Baeschlin DK J Med Chem. 2013 Jan 29. PMID:23360239<ref>PMID:23360239</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4gja" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 06:59, 26 October 2022

OCA — Wed, 26 Oct 2022 06:59:49 GMT

←Older revision		Revision as of 06:59, 26 October 2022
Line 1:		Line 1:

	==Crystal structure of renin in complex with NVP-AYL747 (compound 5)==		==Crystal structure of renin in complex with NVP-AYL747 (compound 5)==
-	<StructureSection load='4gja' size='340' side='right' caption='[[4gja]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='4gja' size='340' side='right'caption='[[4gja]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gja]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4GJA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gja]] 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=4GJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GJA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0M3:(3S,5R)-N-(2,2-DIPHENYLETHYL)-5-{[(4-METHYLPHENYL)SULFONYL]AMINO}PIPERIDINE-3-CARBOXAMIDE'>0M3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0M3:(3S,5R)-N-(2,2-DIPHENYLETHYL)-5-{[(4-METHYLPHENYL)SULFONYL]AMINO}PIPERIDINE-3-CARBOXAMIDE'>0M3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gj8\|4gj8]], [[4gj9\|4gj9]], [[4gjb\|4gjb]], [[4gjc\|4gjc]], [[4gjd\|4gjd]]</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=4gja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gja OCA], [https://pdbe.org/4gja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gja RCSB], [https://www.ebi.ac.uk/pdbsum/4gja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gja ProSAT]</span></td></tr>
-	~~<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=4gja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gja OCA], [~~http~~://pdbe.org/4gja PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4gja RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4gja PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4gja ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== 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>	+	[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 ==		== 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.	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 30:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Renin~~]]	+	[[Category: Large Structures]]
-	[[Category: Kroemer, M]]	+	[[Category: Kroemer M]]
-	[[Category: Ostermann, N]]	+	[[Category: Ostermann N]]
-	[[Category: Zink, F]]	+	[[Category: Zink F]]
-	~~[[Category: 5-disubstituted piperidine]]~~	+
-	~~[[Category: Fragment based screening]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Renin inhibitor~~]]	+

OCA at 12:54, 11 August 2016

OCA — Thu, 11 Aug 2016 12:54:27 GMT

←Older revision		Revision as of 12:54, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of renin in complex with NVP-AYL747 (compound 5)==		==Crystal structure of renin in complex with NVP-AYL747 (compound 5)==
	<StructureSection load='4gja' size='340' side='right' caption='[[4gja]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4gja' size='340' side='right' caption='[[4gja]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gja]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GJA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gja]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GJA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0M3:(3S,5R)-N-(2,2-DIPHENYLETHYL)-5-{[(4-METHYLPHENYL)SULFONYL]AMINO}PIPERIDINE-3-CARBOXAMIDE'>0M3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0M3:(3S,5R)-N-(2,2-DIPHENYLETHYL)-5-{[(4-METHYLPHENYL)SULFONYL]AMINO}PIPERIDINE-3-CARBOXAMIDE'>0M3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gj8\|4gj8]], [[4gj9\|4gj9]], [[4gjb\|4gjb]], [[4gjc\|4gjc]], [[4gjd\|4gjd]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gj8\|4gj8]], [[4gj9\|4gj9]], [[4gjb\|4gjb]], [[4gjc\|4gjc]], [[4gjd\|4gjd]]</td></tr>
-	<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 ~~Homo sapiens~~])</td></tr>	+	<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='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=4gja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gja OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gja RCSB], [http://www.ebi.ac.uk/pdbsum/4gja 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=4gja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gja OCA], [http://pdbe.org/4gja PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gja RCSB], [http://www.ebi.ac.uk/pdbsum/4gja PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gja ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4gja" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Renin]]		[[Category: Renin]]
	[[Category: Kroemer, M]]		[[Category: Kroemer, M]]

OCA at 10:33, 20 January 2015

OCA — Tue, 20 Jan 2015 10:33:09 GMT

←Older revision		Revision as of 10:33, 20 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4gja\| PDB=4gja \| SCENE= }}~~	+	==Crystal structure of renin in complex with NVP-AYL747 (compound 5)==
-	===Crystal structure of renin in complex with NVP-AYL747 (compound 5)===	+	<StructureSection load='4gja' size='340' side='right' caption='[[4gja]], [[Resolution\|resolution]] 2.60Å' scene=''>
-	{~~{ABSTRACT_PUBMED_23360239}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4gja]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GJA FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0M3:(3S,5R)-N-(2,2-DIPHENYLETHYL)-5-{[(4-METHYLPHENYL)SULFONYL]AMINO}PIPERIDINE-3-CARBOXAMIDE'>0M3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gj8\|4gj8]], [[4gj9\|4gj9]], [[4gjb\|4gjb]], [[4gjc\|4gjc]], [[4gjd\|4gjd]]</td></tr>
		+	<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 Homo sapiens])</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=4gja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gja OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gja RCSB], [http://www.ebi.ac.uk/pdbsum/4gja 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>		[[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 ==
		+	A small library of fragments comprising putative recognition motifs for the catalytic dyad of aspartic proteases was generated by in silico similarity searches within the corporate compound deck based on rh-renin active site docking and scoring filters. Subsequent screening by NMR identified the low-affinity hits 3 and 4 as competitive active site binders, which could be shown by X-ray crystallography to bind to the hydrophobic S3-S1 pocket of rh-renin. As part of a parallel multiple hit-finding approach, the 3,5-disubstituted piperidine (rac)-5 was discovered by HTS using a enzymatic assay. X-ray crystallography demonstrated the eutomer (3S,5R)-5 to be a peptidomimetic inhibitor binding to a nonsubstrate topography of the rh-renin prime site. The design of the potent and selective (3S,5R)-12 bearing a P3sp-tethered tricyclic P3-P1 pharmacophore derived from 3 is described. (3S,5R)-12 showed oral bioavailability in rats and demonstrated blood pressure lowering activity in the double-transgenic rat model.

-	~~==Function==~~	+	A Novel Class of Oral Direct Renin Inhibitors: Highly Potent 3,5-Disubstituted Piperidines bearing a Tricyclic P3-P1 Pharmacophore.,Ostermann N, Ruedisser S, Ehrhardt C, Breitenstein W, Marzinzik AL, Jacoby E, Vangrevelinghe E, Ottl J, Klumpp M, Hartwieg C, Cumin F, Hassiepen U, Trappe J, Sedrani RC, Geisse S, Gerhartz B, Richert P, Francotte E, Wagner T, Kromer M, Kosaka T, Webb RL, Rigel DF, Maibaum JK, Baeschlin DK J Med Chem. 2013 Jan 29. PMID:23360239<ref>PMID:23360239</ref>
-	~~[[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~~.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4gja]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	<references ~~group="xtra"~~/><~~references~~/>	+	*[[Renin\|Renin]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Renin]]		[[Category: Renin]]
-	[[Category: Kroemer, M.]]	+	[[Category: Kroemer, M]]
-	[[Category: Ostermann, N.]]	+	[[Category: Ostermann, N]]
-	[[Category: Zink, F.]]	+	[[Category: Zink, F]]
	[[Category: 5-disubstituted piperidine]]		[[Category: 5-disubstituted piperidine]]
	[[Category: Fragment based screening]]		[[Category: Fragment based screening]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Renin inhibitor]]		[[Category: Renin inhibitor]]

OCA at 21:46, 10 April 2013

OCA — Wed, 10 Apr 2013 21:46:08 GMT

←Older revision		Revision as of 21:46, 10 April 2013
Line 1:		Line 1:
-	[[Image:4gja.jpg\|left\|200px]]
-
	{{STRUCTURE_4gja\| PDB=4gja \| SCENE= }}		{{STRUCTURE_4gja\| PDB=4gja \| SCENE= }}
-
	===Crystal structure of renin in complex with NVP-AYL747 (compound 5)===		===Crystal structure of renin in complex with NVP-AYL747 (compound 5)===
-
	{{ABSTRACT_PUBMED_23360239}}		{{ABSTRACT_PUBMED_23360239}}
		+
		+	==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.

	==About this Structure==		==About this Structure==
	[[4gja]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA].		[[4gja]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Renin]]		[[Category: Renin]]

OCA at 10:29, 13 February 2013

OCA — Wed, 13 Feb 2013 10:29:12 GMT

←Older revision		Revision as of 10:29, 13 February 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4gja.jpg\|left\|200px]]

-	~~The entry~~ 4gja ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4gja\| PDB=4gja \| SCENE= }}

-	~~Authors: Ostermann, N., Zink, F., Kroemer, M.~~	+	===Crystal structure of renin in complex with NVP-AYL747 (compound 5)===

-	~~Description: Crystal~~ structure ~~of renin in complex~~ with ~~NVP~~-~~AYL747 (compound~~ 5)	+	{{ABSTRACT_PUBMED_23360239}}
		+
		+	==About this Structure==
		+	[[4gja]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GJA OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Renin]]
		+	[[Category: Kroemer, M.]]
		+	[[Category: Ostermann, N.]]
		+	[[Category: Zink, F.]]
		+	[[Category: 5-disubstituted piperidine]]
		+	[[Category: Fragment based screening]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Renin inhibitor]]

OCA at 07:05, 24 October 2012

OCA — Wed, 24 Oct 2012 07:05:06 GMT

←Older revision		Revision as of 07:05, 24 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4gja is ON HOLD	+	The entry 4gja is ON HOLD until Paper Publication

	Authors: Ostermann, N., Zink, F., Kroemer, M.		Authors: Ostermann, N., Zink, F., Kroemer, M.

	Description: Crystal structure of renin in complex with NVP-AYL747 (compound 5)		Description: Crystal structure of renin in complex with NVP-AYL747 (compound 5)

OCA: Protected "4gja" [edit=sysop:move=sysop]

OCA — Wed, 15 Aug 2012 05:28:24 GMT

Protected "4gja" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:28, 15 August 2012

OCA: New page: '''Unreleased structure''' The entry 4gja is ON HOLD Authors: Ostermann, N., Zink, F., Kroemer, M. Description: Crystal structure of renin in complex with NVP-AYL747 (compound 5)

OCA — Wed, 15 Aug 2012 05:28:23 GMT

New page: '''Unreleased structure''' The entry 4gja is ON HOLD Authors: Ostermann, N., Zink, F., Kroemer, M. Description: Crystal structure of renin in complex with NVP-AYL747 (compound 5)

New page

'''Unreleased structure'''

The entry 4gja is ON HOLD

Authors: Ostermann, N., Zink, F., Kroemer, M.

Description: Crystal structure of renin in complex with NVP-AYL747 (compound 5)