3cdb - Revision history

OCA at 09:34, 21 February 2024

2024-02-21T09:34:44Z

←Older revision		Revision as of 09:34, 21 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cdb]] 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=3CDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CDB FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cdb]] 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=3CDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CDB FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=9HI:(3R,5R)~~-~~7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4~~,~~5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</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]] 2.3Å</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]], [[3cd7\|3cd7]], [[3cda\|3cda]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9HI:(3R,5R)-7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4,5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [https://pdbe.org/3cdb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [https://www.ebi.ac.uk/pdbsum/3cdb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cdb 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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [https://pdbe.org/3cdb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [https://www.ebi.ac.uk/pdbsum/3cdb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cdb 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]]
Line 22:		Line 20:
	</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=3cdb 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=3cdb 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 3cdb" 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

2021-10-20T19:09:21Z

←Older revision		Revision as of 19:09, 20 October 2021
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='3cdb' size='340' side='right' caption='[[3cdb]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='3cdb' size='340' side='right'caption='[[3cdb]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3cdb]] 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=3CDB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3CDB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3cdb]] 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=3CDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CDB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HI:(3R,5R)-7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4,5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9HI:(3R,5R)-7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4,5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</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]], [[3cd7\|3cd7]], [[3cda\|3cda]]</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]], [[3cd7\|3cd7]], [[3cda\|3cda]]</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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [~~http~~://pdbe.org/3cdb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3cdb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3cdb 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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [https://pdbe.org/3cdb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [https://www.ebi.ac.uk/pdbsum/3cdb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cdb 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/3cdb_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/3cdb_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 3cdb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3cdb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[HMG-CoA Reductase 3D structures\|HMG-CoA Reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 36:		Line 39:
	</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

2017-10-25T08:24:55Z

←Older revision		Revision as of 08:24, 25 October 2017
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 3cdb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3cdb" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[HMG-CoA Reductase\|HMG-CoA Reductase]]
	== References ==		== References ==
	<references/>		<references/>
Line 43:		Line 40:
	[[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 14:22, 5 August 2016

2016-08-05T14:22:14Z

←Older revision		Revision as of 14:22, 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='3cdb' size='340' side='right' caption='[[3cdb]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='3cdb' size='340' side='right' caption='[[3cdb]], [[Resolution\|resolution]] 2.30Å' 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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [http://www.ebi.ac.uk/pdbsum/3cdb 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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [http://pdbe.org/3cdb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [http://www.ebi.ac.uk/pdbsum/3cdb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cdb 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=3cdb 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 3cdb" style="background-color:#fffaf0;"></div>

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

OCA at 19:32, 25 December 2014

2014-12-25T19:32:10Z

←Older revision		Revision as of 19:32, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cdb]] 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=3CDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CDB FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cdb]] 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=3CDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CDB FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HI:(3R,5R)-7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4,5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HI:(3R,5R)-7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4,5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</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]], [[3cd7\|3cd7]], [[3cda\|3cda]]</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]], [[3cd7\|3cd7]], [[3cda\|3cda]]</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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [http://www.ebi.ac.uk/pdbsum/3cdb 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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [http://www.ebi.ac.uk/pdbsum/3cdb 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 07:18, 29 September 2014

2014-09-29T07:18:35Z

←Older revision		Revision as of 07:18, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~3cdb.~~png~~\|~~left~~\|200px]]	+	==Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors==
		+	<StructureSection load='3cdb' size='340' side='right' caption='[[3cdb]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3cdb]] 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=3CDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CDB FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HI:(3R,5R)-7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4,5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</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]], [[3cd7\|3cd7]], [[3cda\|3cda]]</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=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [http://www.ebi.ac.uk/pdbsum/3cdb 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/3cdb_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_3cdb\| PDB=3cdb \| 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==~~	+
-	~~[[3cdb]] 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=3CDB 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 20:34, 20 October 2012

2012-10-20T20:34:48Z

←Older revision		Revision as of 20:34, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3cdb]] 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=3CDB OCA].	+	[[3cdb]] 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=3CDB OCA].

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

OCA at 10:57, 27 July 2012

2012-07-27T10:57:20Z

←Older revision		Revision as of 10:57, 27 July 2012
Line 1:		Line 1:
	[[Image:3cdb.png\|left\|200px]]		[[Image:3cdb.png\|left\|200px]]

-	<!--
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-	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.
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	{{STRUCTURE_3cdb\| PDB=3cdb \| SCENE= }}		{{STRUCTURE_3cdb\| PDB=3cdb \| 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.
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	{{ABSTRACT_PUBMED_18540668}}		{{ABSTRACT_PUBMED_18540668}}

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

2012-06-02T15:26:58Z

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

←Older revision

Revision as of 15:26, 2 June 2012