6xz8 - Revision history

OCA at 07:39, 1 May 2024

OCA — Wed, 01 May 2024 07:39:49 GMT

←Older revision		Revision as of 07:39, 1 May 2024
Line 3:		Line 3:
	<StructureSection load='6xz8' size='340' side='right'caption='[[6xz8]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='6xz8' size='340' side='right'caption='[[6xz8]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6xz8]] is a 3 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=6XZ8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6XZ8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xz8]] is a 3 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=6XZ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XZ8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=O4T:~{N}-[(1~{R})-1-[5-(6-chloranyl-1,1-dimethyl-3-oxidanylidene-isoindol-2-yl)pyridin-3-yl]ethyl]methanesulfonamide'>O4T</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]] 3Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP11B2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=O4T:~{N}-[(1~{R})-1-[5-(6-chloranyl-1,1-dimethyl-3-oxidanylidene-isoindol-2-yl)pyridin-3-yl]ethyl]methanesulfonamide'>O4T</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6xz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xz8 OCA], [~~http~~://pdbe.org/6xz8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6xz8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6xz8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6xz8 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=6xz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xz8 OCA], [https://pdbe.org/6xz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xz8 RCSB], [https://www.ebi.ac.uk/pdbsum/6xz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xz8 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/C11B2_HUMAN C11B2_HUMAN]] Familial hyperreninemic hypoaldosteronism type 1;Familial hyperaldosteronism type I. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The molecular defect causing hyperaldosteronism familial 1 is an anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2.	+	[https://www.uniprot.org/uniprot/C11B2_HUMAN C11B2_HUMAN] Familial hyperreninemic hypoaldosteronism type 1;Familial hyperaldosteronism type I. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The molecular defect causing hyperaldosteronism familial 1 is an anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/C11B2_HUMAN C11B2_HUMAN]] Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.<ref>PMID:23322723</ref>	+	[https://www.uniprot.org/uniprot/C11B2_HUMAN C11B2_HUMAN] Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.<ref>PMID:23322723</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Aldosterone synthase (CYP11B2) inhibitors were explored in recent years as an alternative therapeutic option to MR antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including heart, vasculature, kidney, and CNS. A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 44, in an in vivo cynomolgus monkey acute ACTH challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1.	+
-		+
-	Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors.,Liu Y, Wu J, Zhou M, Chen W, Li D, Wang ZG, Hornsperger B, Aebi JD, Marki HP, Kuhn B, Wang L, Kuglstatter A, Benz J, Muller S, Hochstrasser R, Ottaviani G, Xin J, Kirchner S, Mohr S, Verry P, Riboulet W, Shen HC, Mayweg AV, Amrein K, Tan X J Med Chem. 2020 Jun 12. doi: 10.1021/acs.jmedchem.0c00233. PMID:32530624<ref>PMID:32530624</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6xz8" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 28:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Benz, J]]	+	[[Category: Benz J]]
-	[[Category: Joseph, C]]	+	[[Category: Joseph C]]
-	[[Category: Kuglstatter, A]]	+	[[Category: Kuglstatter A]]
-	~~[[Category: Aldosterone synthase]]~~	+
-	~~[[Category: Cyp11b2]]~~	+
-	~~[[Category: Cytochrome p450]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 11:47, 22 July 2020

OCA — Wed, 22 Jul 2020 11:47:10 GMT

←Older revision		Revision as of 11:47, 22 July 2020
Line 1:		Line 1:

	==Structure of aldosterone synthase (CYP11B2) in complex with N-[(1R)-1-[5-(6-chloro-1,1-dimethyl-3-oxo-isoindolin-2-yl)-3-pyridyl]ethyl]methanesulfonamide==		==Structure of aldosterone synthase (CYP11B2) in complex with N-[(1R)-1-[5-(6-chloro-1,1-dimethyl-3-oxo-isoindolin-2-yl)-3-pyridyl]ethyl]methanesulfonamide==
-	<StructureSection load='6xz8' size='340' side='right'caption='[[6xz8]]' scene=''>	+	<StructureSection load='6xz8' size='340' side='right'caption='[[6xz8]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XZ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XZ8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xz8]] is a 3 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=6XZ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XZ8 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xz8 OCA], [http://pdbe.org/6xz8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xz8 RCSB], [http://www.ebi.ac.uk/pdbsum/6xz8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xz8 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=O4T:~{N}-[(1~{R})-1-[5-(6-chloranyl-1,1-dimethyl-3-oxidanylidene-isoindol-2-yl)pyridin-3-yl]ethyl]methanesulfonamide'>O4T</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP11B2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xz8 OCA], [http://pdbe.org/6xz8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xz8 RCSB], [http://www.ebi.ac.uk/pdbsum/6xz8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xz8 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/C11B2_HUMAN C11B2_HUMAN]] Familial hyperreninemic hypoaldosteronism type 1;Familial hyperaldosteronism type I. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The molecular defect causing hyperaldosteronism familial 1 is an anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/C11B2_HUMAN C11B2_HUMAN]] Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.<ref>PMID:23322723</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aldosterone synthase (CYP11B2) inhibitors were explored in recent years as an alternative therapeutic option to MR antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including heart, vasculature, kidney, and CNS. A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 44, in an in vivo cynomolgus monkey acute ACTH challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1.
		+
		+	Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors.,Liu Y, Wu J, Zhou M, Chen W, Li D, Wang ZG, Hornsperger B, Aebi JD, Marki HP, Kuhn B, Wang L, Kuglstatter A, Benz J, Muller S, Hochstrasser R, Ottaviani G, Xin J, Kirchner S, Mohr S, Verry P, Riboulet W, Shen HC, Mayweg AV, Amrein K, Tan X J Med Chem. 2020 Jun 12. doi: 10.1021/acs.jmedchem.0c00233. PMID:32530624<ref>PMID:32530624</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xz8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Benz J]]	+	[[Category: Benz, J]]
-	[[Category: Joseph C]]	+	[[Category: Joseph, C]]
-	[[Category: Kuglstatter A]]	+	[[Category: Kuglstatter, A]]
		+	[[Category: Aldosterone synthase]]
		+	[[Category: Cyp11b2]]
		+	[[Category: Cytochrome p450]]
		+	[[Category: Oxidoreductase]]

OCA at 06:31, 25 June 2020

OCA — Thu, 25 Jun 2020 06:31:42 GMT

←Older revision		Revision as of 06:31, 25 June 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6xz8 is ~~ON HOLD~~	+	==Structure of aldosterone synthase (CYP11B2) in complex with N-[(1R)-1-[5-(6-chloro-1,1-dimethyl-3-oxo-isoindolin-2-yl)-3-pyridyl]ethyl]methanesulfonamide==
-		+	<StructureSection load='6xz8' size='340' side='right'caption='[[6xz8]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XZ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XZ8 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xz8 OCA], [http://pdbe.org/6xz8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xz8 RCSB], [http://www.ebi.ac.uk/pdbsum/6xz8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xz8 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Benz J]]
		+	[[Category: Joseph C]]
		+	[[Category: Kuglstatter A]]

OCA: Protected "6xz8" [edit=sysop:move=sysop]

OCA — Thu, 13 Feb 2020 02:53:11 GMT

Protected "6xz8" [edit=sysop:move=sysop]

←Older revision

Revision as of 02:53, 13 February 2020

OCA: New page: '''Unreleased structure''' The entry 6xz8 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 13 Feb 2020 02:53:09 GMT

New page: '''Unreleased structure''' The entry 6xz8 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6xz8 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]