4gj6 - Revision history

OCA at 15:48, 14 March 2024

2024-03-14T15:48:23Z

←Older revision		Revision as of 15:48, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4gj6]] 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=4GJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GJ6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4gj6]] 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=4GJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GJ6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LS:N-{[(3S,4S)-4-BENZYLPYRROLIDIN-3-YL]METHYL}-4-CHLORO-N-PHENYLANILINE'>0LS</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]] 2.58Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LS:N-{[(3S,4S)-4-BENZYLPYRROLIDIN-3-YL]METHYL}-4-CHLORO-N-PHENYLANILINE'>0LS</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=4gj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gj6 OCA], [https://pdbe.org/4gj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gj6 RCSB], [https://www.ebi.ac.uk/pdbsum/4gj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gj6 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=4gj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gj6 OCA], [https://pdbe.org/4gj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gj6 RCSB], [https://www.ebi.ac.uk/pdbsum/4gj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gj6 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 ==
-	The small-molecule trans-3,4-disubstituted pyrrolidine 6 was identified from in silico three-dimensional (3D) pharmacophore searches based on known X-ray structures of renin-inhibitor complexes and demonstrated to be a weakly active inhibitor of the human enzyme. The unexpected binding mode of the more potent enantiomer (3S,4S)-6a in an extended conformation spanning the non-prime and S1' pockets of the rh-renin active site was elucidated by X-ray crystallography. Initial structure-activity relationship work focused on modifications of the hydrophobic diphenylamine portion positioned in S1 and extending toward the S2 pocket. Replacement with an optimized P3-P1 pharmacophore interacting to the nonsubstrate S3sp cavity eventually resulted in significantly improved in vitro potency and selectivity. The prototype analogue (3S,4S)-12a of this new class of direct renin inhibitors exerted blood pressure lowering effects in a hypertensive double-transgenic rat model after oral administration.
-
-	The Discovery of Novel Potent trans-3,4-Disubstituted Pyrrolidine Inhibitors of the Human Aspartic Protease Renin from in silico Three-Dimensional (3D) Pharmacophore Searches.,Lorthiois E, Breitenstein W, Cumin F, Ehrhardt C, Francotte E, Jacoby E, Ostermann N, Sellner H, Kosaka T, Webb R, Rigel D, Hassiepen U, Richert P, Wagner T, Maibaum JK J Med Chem. 2013 Feb 20. PMID:23425156<ref>PMID:23425156</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4gj6" style="background-color:#fffaf0;"></div>

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

OCA at 06:59, 26 October 2022

2022-10-26T06:59:31Z

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

	==Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)==		==Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)==
-	<StructureSection load='4gj6' size='340' side='right' caption='[[4gj6]], [[Resolution\|resolution]] 2.58Å' scene=''>	+	<StructureSection load='4gj6' size='340' side='right'caption='[[4gj6]], [[Resolution\|resolution]] 2.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gj6]] 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=4GJ6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4GJ6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gj6]] 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=4GJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GJ6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LS:N-{[(3S,4S)-4-BENZYLPYRROLIDIN-3-YL]METHYL}-4-CHLORO-N-PHENYLANILINE'>0LS</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=0LS:N-{[(3S,4S)-4-BENZYLPYRROLIDIN-3-YL]METHYL}-4-CHLORO-N-PHENYLANILINE'>0LS</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">[[4gj5\|4gj5]], [[4gj7\|4gj7]]</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=4gj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gj6 OCA], [https://pdbe.org/4gj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gj6 RCSB], [https://www.ebi.ac.uk/pdbsum/4gj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gj6 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=4gj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gj6 OCA], [~~http~~://pdbe.org/4gj6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4gj6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4gj6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4gj6 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: 4-disubstituted pyrrolidine]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Pharmacophore search]]~~	+
-	~~[[Category: Renin inhibitor]]~~	+
-	~~[[Category: Trans-3~~]]	+

OCA at 08:40, 11 August 2016

2016-08-11T08:40:24Z

←Older revision		Revision as of 08:40, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)==		==Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)==
	<StructureSection load='4gj6' size='340' side='right' caption='[[4gj6]], [[Resolution\|resolution]] 2.58Å' scene=''>		<StructureSection load='4gj6' size='340' side='right' caption='[[4gj6]], [[Resolution\|resolution]] 2.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gj6]] 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=4GJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GJ6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gj6]] 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=4GJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GJ6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LS:N-{[(3S,4S)-4-BENZYLPYRROLIDIN-3-YL]METHYL}-4-CHLORO-N-PHENYLANILINE'>0LS</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=0LS:N-{[(3S,4S)-4-BENZYLPYRROLIDIN-3-YL]METHYL}-4-CHLORO-N-PHENYLANILINE'>0LS</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">[[4gj5\|4gj5]], [[4gj7\|4gj7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gj5\|4gj5]], [[4gj7\|4gj7]]</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=4gj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gj6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gj6 RCSB], [http://www.ebi.ac.uk/pdbsum/4gj6 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=4gj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gj6 OCA], [http://pdbe.org/4gj6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gj6 RCSB], [http://www.ebi.ac.uk/pdbsum/4gj6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gj6 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 4gj6" 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 09:36, 20 January 2015

2015-01-20T09:36:09Z

←Older revision		Revision as of 09:36, 20 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4gj6\| PDB=4gj6 \| SCENE= }}~~	+	==Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)==
-	===Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)===	+	<StructureSection load='4gj6' size='340' side='right' caption='[[4gj6]], [[Resolution\|resolution]] 2.58Å' scene=''>
-	{~~{ABSTRACT_PUBMED_23425156}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4gj6]] 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=4GJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GJ6 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LS:N-{[(3S,4S)-4-BENZYLPYRROLIDIN-3-YL]METHYL}-4-CHLORO-N-PHENYLANILINE'>0LS</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">[[4gj5\|4gj5]], [[4gj7\|4gj7]]</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=4gj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gj6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gj6 RCSB], [http://www.ebi.ac.uk/pdbsum/4gj6 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 ==
		+	The small-molecule trans-3,4-disubstituted pyrrolidine 6 was identified from in silico three-dimensional (3D) pharmacophore searches based on known X-ray structures of renin-inhibitor complexes and demonstrated to be a weakly active inhibitor of the human enzyme. The unexpected binding mode of the more potent enantiomer (3S,4S)-6a in an extended conformation spanning the non-prime and S1' pockets of the rh-renin active site was elucidated by X-ray crystallography. Initial structure-activity relationship work focused on modifications of the hydrophobic diphenylamine portion positioned in S1 and extending toward the S2 pocket. Replacement with an optimized P3-P1 pharmacophore interacting to the nonsubstrate S3sp cavity eventually resulted in significantly improved in vitro potency and selectivity. The prototype analogue (3S,4S)-12a of this new class of direct renin inhibitors exerted blood pressure lowering effects in a hypertensive double-transgenic rat model after oral administration.

-	~~==Function==~~	+	The Discovery of Novel Potent trans-3,4-Disubstituted Pyrrolidine Inhibitors of the Human Aspartic Protease Renin from in silico Three-Dimensional (3D) Pharmacophore Searches.,Lorthiois E, Breitenstein W, Cumin F, Ehrhardt C, Francotte E, Jacoby E, Ostermann N, Sellner H, Kosaka T, Webb R, Rigel D, Hassiepen U, Richert P, Wagner T, Maibaum JK J Med Chem. 2013 Feb 20. PMID:23425156<ref>PMID:23425156</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>
-	~~[[4gj6]] 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=4GJ6 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: 4-disubstituted pyrrolidine]]		[[Category: 4-disubstituted pyrrolidine]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 21:54, 10 April 2013

2013-04-10T21:54:53Z

←Older revision		Revision as of 21:54, 10 April 2013
Line 1:		Line 1:
-	[[Image:4gj6.jpg\|left\|200px]]
-
	{{STRUCTURE_4gj6\| PDB=4gj6 \| SCENE= }}		{{STRUCTURE_4gj6\| PDB=4gj6 \| SCENE= }}
-
	===Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)===		===Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)===
-
	{{ABSTRACT_PUBMED_23425156}}		{{ABSTRACT_PUBMED_23425156}}
		+
		+	==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==
	[[4gj6]] 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=4GJ6 OCA].		[[4gj6]] 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=4GJ6 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Renin]]		[[Category: Renin]]

OCA at 14:14, 6 March 2013

2013-03-06T14:14:32Z

←Older revision		Revision as of 14:14, 6 March 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4gj6.jpg\|left\|200px]]

-	~~The entry~~ 4gj6 ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4gj6\| PDB=4gj6 \| SCENE= }}

-	~~Authors: Ostermann, N., Zink, F., Kroemer, M.~~	+	===Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)===

-	~~Description: Crystal~~ structure ~~of renin in complex~~ with ~~NVP~~-~~AYZ832 (compound 6a)~~	+	{{ABSTRACT_PUBMED_23425156}}
		+
		+	==About this Structure==
		+	[[4gj6]] 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=4GJ6 OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Renin]]
		+	[[Category: Kroemer, M.]]
		+	[[Category: Ostermann, N.]]
		+	[[Category: Zink, F.]]
		+	[[Category: 4-disubstituted pyrrolidine]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Pharmacophore search]]
		+	[[Category: Renin inhibitor]]
		+	[[Category: Trans-3]]

OCA at 07:04, 24 October 2012

2012-10-24T07:04:59Z

←Older revision		Revision as of 07:04, 24 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4gj6 is ON HOLD	+	The entry 4gj6 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-AYZ832 (compound 6a)		Description: Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)

OCA: Protected "4gj6" [edit=sysop:move=sysop]

2012-08-15T05:28:17Z

Protected "4gj6" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:28, 15 August 2012

OCA: New page: '''Unreleased structure''' The entry 4gj6 is ON HOLD Authors: Ostermann, N., Zink, F., Kroemer, M. Description: Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)

2012-08-15T05:28:16Z

New page: '''Unreleased structure''' The entry 4gj6 is ON HOLD Authors: Ostermann, N., Zink, F., Kroemer, M. Description: Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)

New page

'''Unreleased structure'''

The entry 4gj6 is ON HOLD

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

Description: Crystal structure of renin in complex with NVP-AYZ832 (compound 6a)