3cd7 - Revision history

OCA at 09:34, 21 February 2024

2024-02-21T09:34:42Z

← Older revision		Revision as of 09:34, 21 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cd7]] is a 4 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=3CD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CD7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cd7]] is a 4 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=3CD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CD7 FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]~~-3,~~5-DIHYDROXYHEPTANOIC+ACID'>882</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]] 2.05Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[3cct\|3cct]], [[3ccw\|3ccw]], [[3ccz\|3ccz]], [[3cd0\|3cd0]], [[3cd5\|3cd5]], [[3cda\|3cda]], [[3cdb\|3cdb]]</div>~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene></td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>HMGCR ([https://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'>~~[~~https://en.wikipedia.org/wiki/Hydroxymethylglutaryl~~-~~CoA_reductase_~~(~~NADPH~~) ~~Hydroxymethylglutaryl~~-~~CoA reductase~~ (~~NADPH~~)], ~~with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34]~~ </~~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=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [https://pdbe.org/3cd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [https://www.ebi.ac.uk/pdbsum/3cd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cd7 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=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [https://pdbe.org/3cd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [https://www.ebi.ac.uk/pdbsum/3cd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cd7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/HMDH_HUMAN HMDH_HUMAN]] Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.		[https://www.uniprot.org/uniprot/HMDH_HUMAN HMDH_HUMAN] Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cd7 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cd7 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2-7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC 50 = 7.9 nM) inhibitor with excellent hepatoselectivity (>1000-fold) and good in vivo efficacy. The binding of 1 to HMGR was found to be enthalpically driven with a Delta H of -17.7 kcal/M. Additionally, a second novel series of bicyclic pyrrole-based inhibitors was identified that induced order in a protein flap of HMGR. Similar ordering was detected in a substrate complex, but has not been reported in previous statin inhibitor complexes with HMGR.

	Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase.,Sarver RW, Bills E, Bolton G, Bratton LD, Caspers NL, Dunbar JB, Harris MS, Hutchings RH, Kennedy RM, Larsen SD, Pavlovsky A, Pfefferkorn JA, Bainbridge G J Med Chem. 2008 Jun 10;. PMID:18540668<ref>PMID:18540668</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3cd7" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[HMG-CoA Reductase 3D structures\|HMG-CoA Reductase 3D structures]]		*[[HMG-CoA Reductase 3D structures\|HMG-CoA Reductase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Finzel~~, B C~~]]		[[Category: Finzel BC]]
	[[Category: Harris~~, M S~~]]		[[Category: Harris MS]]
	[[Category: Pavlovsky, A]]		[[Category: Pavlovsky A]]
	[[Category: Sarver~~, R W]]~~		[[Category: Sarver RW]]
	~~[[Category: Alternative splicing]]~~
	~~[[Category: Cholesterol biosynthesis]]~~
	~~[[Category: Endoplasmic reticulum]]~~
	~~[[Category: Glycoprotein]]~~
	~~[[Category: Hmg-coa]]~~
	~~[[Category: Lipid synthesis]]~~
	~~[[Category: Membrane]]~~
	~~[[Category: Nadph]]~~
	~~[[Category: Oxidoreductase]]~~
	~~[[Category: Peroxisome]]~~
	~~[[Category: Polymorphism]]~~
	~~[[Category: Statin]]~~
	~~[[Category: Steroid biosynthesis]]~~
	~~[[Category: Transmembrane~~]]

OCA at 19:09, 20 October 2021

2021-10-20T19:09:06Z

← Older revision		Revision as of 19:09, 20 October 2021
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	==Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors==		==Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors==
	<StructureSection load='3cd7' size='340' side='right' caption='[[3cd7]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='3cd7' size='340' side='right'caption='[[3cd7]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cd7]] is a 4 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=3CD7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3CD7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cd7]] is a 4 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=3CD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CD7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cct\|3cct]], [[3ccw\|3ccw]], [[3ccz\|3ccz]], [[3cd0\|3cd0]], [[3cd5\|3cd5]], [[3cda\|3cda]], [[3cdb\|3cdb]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3cct\|3cct]], [[3ccw\|3ccw]], [[3ccz\|3ccz]], [[3cd0\|3cd0]], [[3cd5\|3cd5]], [[3cda\|3cda]], [[3cdb\|3cdb]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMGCR ([~~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">HMGCR ([https://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/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </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=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [~~http~~://pdbe.org/3cd7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3cd7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3cd7 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=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [https://pdbe.org/3cd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [https://www.ebi.ac.uk/pdbsum/3cd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cd7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/HMDH_HUMAN HMDH_HUMAN]] Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.		[[https://www.uniprot.org/uniprot/HMDH_HUMAN HMDH_HUMAN]] Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/3cd7_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/3cd7_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 3cd7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3cd7" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[HMG-CoA Reductase 3D structures\|HMG-CoA Reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
			[[Category: Large Structures]]
	[[Category: Finzel, B C]]		[[Category: Finzel, B C]]
	[[Category: Harris, M S]]		[[Category: Harris, M S]]

OCA at 08:24, 25 October 2017

2017-10-25T08:24:42Z

← Older revision		Revision as of 08:24, 25 October 2017
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 3cd7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3cd7" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[HMG-CoA Reductase\|HMG-CoA Reductase]]
	== References ==		== References ==
	<references/>		<references/>
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	[[Category: Pavlovsky, A]]		[[Category: Pavlovsky, A]]
	[[Category: Sarver, R W]]		[[Category: Sarver, R W]]
			[[Category: Alternative splicing]]
	[[Category: Cholesterol biosynthesis]]		[[Category: Cholesterol biosynthesis]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]
Line 52:		Line 50:
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Peroxisome]]		[[Category: Peroxisome]]
			[[Category: Polymorphism]]
	[[Category: Statin]]		[[Category: Statin]]
	[[Category: Steroid biosynthesis]]		[[Category: Steroid biosynthesis]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]

OCA at 01:35, 5 August 2016

2016-08-05T01:35:14Z

← Older revision		Revision as of 01:35, 5 August 2016
Line 1:		Line 1:

	==Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors==		==Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors==
	<StructureSection load='3cd7' size='340' side='right' caption='[[3cd7]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='3cd7' size='340' side='right' caption='[[3cd7]], [[Resolution\|resolution]] 2.05Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMGCR ([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">HMGCR ([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/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </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=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [http://www.ebi.ac.uk/pdbsum/3cd7 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=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [http://pdbe.org/3cd7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [http://www.ebi.ac.uk/pdbsum/3cd7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cd7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cd7 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 30:
	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 3cd7" style="background-color:#fffaf0;"></div>

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

OCA at 14:44, 25 December 2014

2014-12-25T14:44:53Z

← Older revision		Revision as of 14:44, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cd7]] is a 4 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=3CD7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CD7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cd7]] is a 4 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=3CD7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CD7 FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cct\|3cct]], [[3ccw\|3ccw]], [[3ccz\|3ccz]], [[3cd0\|3cd0]], [[3cd5\|3cd5]], [[3cda\|3cda]], [[3cdb\|3cdb]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cct\|3cct]], [[3ccw\|3ccw]], [[3ccz\|3ccz]], [[3cd0\|3cd0]], [[3cd5\|3cd5]], [[3cda\|3cda]], [[3cdb\|3cdb]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMGCR ([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">HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </span></td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [http://www.ebi.ac.uk/pdbsum/3cd7 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=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [http://www.ebi.ac.uk/pdbsum/3cd7 PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/HMDH_HUMAN HMDH_HUMAN]] Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Finzel, B C.]]		[[Category: Finzel, B C]]
	[[Category: Harris, M S.]]		[[Category: Harris, M S]]
	[[Category: Pavlovsky, A.]]		[[Category: Pavlovsky, A]]
	[[Category: Sarver, R W.]]		[[Category: Sarver, R W]]
	[[Category: Cholesterol biosynthesis]]		[[Category: Cholesterol biosynthesis]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]

OCA at 09:41, 29 September 2014

2014-09-29T09:41:52Z

← Older revision		Revision as of 09:41, 29 September 2014
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	[[Image:~~3cd7~~.~~png~~\|~~left~~\|~~200px~~]]		==Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors==
			<StructureSection load='3cd7' size='340' side='right' caption='[[3cd7]], [[Resolution\|resolution]] 2.05Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3cd7]] is a 4 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=3CD7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CD7 FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cct\|3cct]], [[3ccw\|3ccw]], [[3ccz\|3ccz]], [[3cd0\|3cd0]], [[3cd5\|3cd5]], [[3cda\|3cda]], [[3cdb\|3cdb]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </span></td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cd7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cd7 RCSB], [http://www.ebi.ac.uk/pdbsum/3cd7 PDBsum]</span></td></tr>
			<table>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/3cd7_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2-7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC 50 = 7.9 nM) inhibitor with excellent hepatoselectivity (>1000-fold) and good in vivo efficacy. The binding of 1 to HMGR was found to be enthalpically driven with a Delta H of -17.7 kcal/M. Additionally, a second novel series of bicyclic pyrrole-based inhibitors was identified that induced order in a protein flap of HMGR. Similar ordering was detected in a substrate complex, but has not been reported in previous statin inhibitor complexes with HMGR.

	~~{{STRUCTURE_3cd7\| PDB=3cd7 \| SCENE= }}~~		Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase.,Sarver RW, Bills E, Bolton G, Bratton LD, Caspers NL, Dunbar JB, Harris MS, Hutchings RH, Kennedy RM, Larsen SD, Pavlovsky A, Pfefferkorn JA, Bainbridge G J Med Chem. 2008 Jun 10;. PMID:18540668<ref>PMID:18540668</ref>

	~~===Thermodynamic and structure guided design~~ of ~~statin hmg-coa reductase inhibitors===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_18540668}}~~

	~~==About this Structure==~~
	~~[[3cd7]] is a 4 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=3CD7 OCA].~~

	==See Also==		==See Also==
	*[[HMG-CoA Reductase\|HMG-CoA Reductase]]		*[[HMG-CoA Reductase\|HMG-CoA Reductase]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:018540668<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Finzel, B C.]]		[[Category: Finzel, B C.]]

OCA at 17:57, 20 October 2012

2012-10-20T17:57:49Z

← Older revision		Revision as of 17:57, 20 October 2012
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	==About this Structure==		==About this Structure==
	[[3cd7]] is a 4 chain structure ~~of [[HMG-CoA Reductase]]~~ 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=3CD7 OCA].		[[3cd7]] is a 4 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=3CD7 OCA].

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

OCA at 02:33, 27 July 2012

2012-07-27T02:33:45Z

← Older revision		Revision as of 02:33, 27 July 2012
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	[[Image:3cd7.png\|left\|200px]]		[[Image:3cd7.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3cd7", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_3cd7\| PDB=3cd7 \| SCENE= }}		{{STRUCTURE_3cd7\| PDB=3cd7 \| SCENE= }}

	===Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors===		===Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_18540668}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 18540668 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_18540668}}		{{ABSTRACT_PUBMED_18540668}}

OCA: Protected "3cd7" [edit=sysop:move=sysop]

2012-06-02T15:18:16Z

Protected "3cd7" [edit=sysop:move=sysop]

← Older revision	Revision as of 15:18, 2 June 2012
(No difference)