3hlc - Revision history

OCA at 10:00, 21 February 2024

2024-02-21T10:00:35Z

← Older revision		Revision as of 10:00, 21 February 2024
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	<StructureSection load='3hlc' size='340' side='right'caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3hlc' size='340' side='right'caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Aspte Aspte~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HLC FirstGlance]. <br>		<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HLC FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>~~, ~~<scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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]] 2Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height~~: ~~3em;~~'>~~[[3hl9\|3hl9]], [[3hlb\|3hlb]], [[3hld\|3hld]]~~</~~div~~></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=3hlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlc OCA], [https://pdbe.org/3hlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlc RCSB], [https://www.ebi.ac.uk/pdbsum/3hlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlc 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=3hlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlc OCA], [https://pdbe.org/3hlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlc RCSB], [https://www.ebi.ac.uk/pdbsum/3hlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlc ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/LOVD_ASPTE LOVD_ASPTE] Monacolin J acid methylbutanoyltransferase; part of the gene cluster that mediates the biosynthesis of lovastatin (also known as mevinolin, mevacor or monacolin K), a hypolipidemic inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) (PubMed:10334994, PubMed:12929390, PubMed:21495633). The first step in the biosynthesis of lovastatin is the production of dihydromonacolin L acid by the lovastatin nonaketide synthase lovB and the trans-acting enoyl reductase lovC via condensation of one acetyl-CoA unit and 8 malonyl-CoA units (PubMed:10334994, PubMed:10381407, PubMed:19900898, PubMed:22733743). Dihydromonacolin L acid is released from lovB by the thioesterase lovG (PubMed:23653178). Next, dihydromonacolin L acid is oxidized by the dihydromonacolin L monooxygenase lovA twice to form monacolin J acid (PubMed:12929390, PubMed:21495633). The 2-methylbutyrate moiety of lovastatin is synthesized by the lovastatin diketide synthase lovF via condensation of one acetyl-CoA unit and one malonyl-CoA unit (PubMed:19530726, PubMed:21069965). Finally, the covalent attachment of this moiety to monacolin J acid is catalyzed by the transesterase lovD to yield lovastatin (PubMed:10334994, PubMed:17113998, PubMed:18988191, PubMed:19875080, PubMed:24727900). LovD has broad substrate specificity and can also convert monacolin J to simvastatin using alpha-dimethylbutanoyl-S-methyl-3-mercaptopropionate (DMB-S-MMP) as the thioester acyl donor, and can also catalyze the reverse reaction and function as hydrolase in vitro (PubMed:19875080). LovD has much higher activity with LovF-bound 2-methylbutanoate than with free diketide substrates (PubMed:21069965).<ref>PMID:10334994</ref> <ref>PMID:10381407</ref> <ref>PMID:12929390</ref> <ref>PMID:17113998</ref> <ref>PMID:18988191</ref> <ref>PMID:19530726</ref> <ref>PMID:19875080</ref> <ref>PMID:19900898</ref> <ref>PMID:21069965</ref> <ref>PMID:21495633</ref> <ref>PMID:22733743</ref> <ref>PMID:23653178</ref> <ref>PMID:24727900</ref>
	== 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=3hlc 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=3hlc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Enzymes from natural product biosynthetic pathways are attractive candidates for creating tailored biocatalysts to produce semisynthetic pharmaceutical compounds. LovD is an acyltransferase that converts the inactive monacolin J acid (MJA) into the cholesterol-lowering lovastatin. LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic alpha-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst. Here we used directed evolution to improve the properties of LovD toward semisynthesis of simvastatin. Mutants with improved catalytic efficiency, solubility, and thermal stability were obtained, with the best mutant displaying an approximately 11-fold increase in an Escherichia coli-based biocatalytic platform. To understand the structural basis of LovD enzymology, seven X-ray crystal structures were determined, including the parent LovD, an improved mutant G5, and G5 cocrystallized with ligands. Comparisons between the structures reveal that beneficial mutations stabilize the structure of G5 in a more compact conformation that is favorable for catalysis.

	Directed evolution and structural characterization of a simvastatin synthase.,Gao X, Xie X, Pashkov I, Sawaya MR, Laidman J, Zhang W, Cacho R, Yeates TO, Tang Y Chem Biol. 2009 Oct 30;16(10):1064-74. PMID:19875080<ref>PMID:19875080</ref>

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

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Aspte~~]]		[[Category: Aspergillus terreus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Gao, X]]		[[Category: Gao X]]
	[[Category: Laidman, J]]		[[Category: Laidman J]]
	[[Category: Pashkov, I]]		[[Category: Pashkov I]]
	[[Category: Sawaya~~, M R~~]]		[[Category: Sawaya MR]]
	[[Category: Tang, Y]]		[[Category: Tang Y]]
	[[Category: Yeates~~, T O]]~~		[[Category: Yeates TO]]
	~~[[Category: Alpha/beta hydrolase fold]]~~
	~~[[Category: Transferase~~]]

OCA at 12:01, 13 October 2021

2021-10-13T12:01:08Z

← Older revision		Revision as of 12:01, 13 October 2021
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	<StructureSection load='3hlc' size='340' side='right'caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3hlc' size='340' side='right'caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Aspte Aspte]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3HLC FirstGlance]. <br>		<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspte Aspte]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HLC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hl9\|3hl9]], [[3hlb\|3hlb]], [[3hld\|3hld]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3hl9\|3hl9]], [[3hlb\|3hlb]], [[3hld\|3hld]]</div></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=3hlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlc OCA], [~~http~~://pdbe.org/3hlc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3hlc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3hlc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlc 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=3hlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlc OCA], [https://pdbe.org/3hlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlc RCSB], [https://www.ebi.ac.uk/pdbsum/3hlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlc ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==

OCA at 07:22, 7 August 2019

2019-08-07T07:22:23Z

← Older revision		Revision as of 07:22, 7 August 2019
Line 1:		Line 1:

	==Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded==		==Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded==
	<StructureSection load='3hlc' size='340' side='right' caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3hlc' size='340' side='right'caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspte Aspte]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HLC FirstGlance]. <br>		<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspte Aspte]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HLC FirstGlance]. <br>
Line 12:		Line 12:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hl/3hlc_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hl/3hlc_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 27:		Line 27:
	</div>		</div>
	<div class="pdbe-citations 3hlc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3hlc" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Simvastatin Synthase\|Simvastatin Synthase]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Aspte]]		[[Category: Aspte]]
			[[Category: Large Structures]]
	[[Category: Gao, X]]		[[Category: Gao, X]]
	[[Category: Laidman, J]]		[[Category: Laidman, J]]

OCA at 07:40, 1 November 2017

2017-11-01T07:40:36Z

← Older revision		Revision as of 07:40, 1 November 2017
Line 27:		Line 27:
	</div>		</div>
	<div class="pdbe-citations 3hlc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3hlc" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Simvastatin Synthase\|Simvastatin Synthase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 02:30, 5 August 2016

2016-08-05T02:30:47Z

← Older revision		Revision as of 02:30, 5 August 2016
Line 1:		Line 1:

	==Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded==		==Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded==
	<StructureSection load='3hlc' size='340' side='right' caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3hlc' size='340' side='right' caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Aspergillus_terreus Aspergillus terreus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HLC FirstGlance]. <br>		<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspte Aspte]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HLC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hl9\|3hl9]], [[3hlb\|3hlb]], [[3hld\|3hld]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hl9\|3hl9]], [[3hlb\|3hlb]], [[3hld\|3hld]]</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=3hlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hlc RCSB], [http://www.ebi.ac.uk/pdbsum/3hlc 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=3hlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlc OCA], [http://pdbe.org/3hlc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hlc RCSB], [http://www.ebi.ac.uk/pdbsum/3hlc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlc ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
Line 15:		Line 16:
	<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=3hlc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 25:		Line 26:
	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 3hlc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 32:		Line 34:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Aspergillus terreus~~]]		[[Category: Aspte]]
	[[Category: Gao, X]]		[[Category: Gao, X]]
	[[Category: Laidman, J]]		[[Category: Laidman, J]]

OCA at 06:01, 18 December 2014

2014-12-18T06:01:50Z

← Older revision		Revision as of 06:01, 18 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3hlc\| PDB=3hlc \| SCENE= }}~~		==Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded==
	===Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded===		<StructureSection load='3hlc' size='340' side='right' caption='[[3hlc]], [[Resolution\|resolution]] 2.00Å' scene=''>
	~~{{ABSTRACT_PUBMED_19875080}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3hlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HLC FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hl9\|3hl9]], [[3hlb\|3hlb]], [[3hld\|3hld]]</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=3hlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hlc RCSB], [http://www.ebi.ac.uk/pdbsum/3hlc 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/hl/3hlc_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 ==
			Enzymes from natural product biosynthetic pathways are attractive candidates for creating tailored biocatalysts to produce semisynthetic pharmaceutical compounds. LovD is an acyltransferase that converts the inactive monacolin J acid (MJA) into the cholesterol-lowering lovastatin. LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic alpha-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst. Here we used directed evolution to improve the properties of LovD toward semisynthesis of simvastatin. Mutants with improved catalytic efficiency, solubility, and thermal stability were obtained, with the best mutant displaying an approximately 11-fold increase in an Escherichia coli-based biocatalytic platform. To understand the structural basis of LovD enzymology, seven X-ray crystal structures were determined, including the parent LovD, an improved mutant G5, and G5 cocrystallized with ligands. Comparisons between the structures reveal that beneficial mutations stabilize the structure of G5 in a more compact conformation that is favorable for catalysis.

	~~==About this Structure==~~		Directed evolution and structural characterization of a simvastatin synthase.,Gao X, Xie X, Pashkov I, Sawaya MR, Laidman J, Zhang W, Cacho R, Yeates TO, Tang Y Chem Biol. 2009 Oct 30;16(10):1064-74. PMID:19875080<ref>PMID:19875080</ref>
	~~[[3hlc]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Aspergillus_terreus Aspergillus terreus]~~. ~~Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=3HLC OCA].~~
			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	==See Also==		==See Also==
	*[[Simvastatin Synthase\|Simvastatin Synthase]]		*[[Simvastatin Synthase\|Simvastatin Synthase]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:019875080<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Aspergillus terreus]]		[[Category: Aspergillus terreus]]
	[[Category: Gao, X.]]		[[Category: Gao, X]]
	[[Category: Laidman, J.]]		[[Category: Laidman, J]]
	[[Category: Pashkov, I.]]		[[Category: Pashkov, I]]
	[[Category: Sawaya, M R.]]		[[Category: Sawaya, M R]]
	[[Category: Tang, Y.]]		[[Category: Tang, Y]]
	[[Category: Yeates, T O.]]		[[Category: Yeates, T O]]
	[[Category: Alpha/beta hydrolase fold]]		[[Category: Alpha/beta hydrolase fold]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 11:15, 11 March 2013

2013-03-11T11:15:12Z

← Older revision		Revision as of 11:15, 11 March 2013
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	~~[[Image:3hlc.png\|left\|200px]]~~

	{{STRUCTURE_3hlc\| PDB=3hlc \| SCENE= }}		{{STRUCTURE_3hlc\| PDB=3hlc \| SCENE= }}

	===Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded===		===Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded===

	{{ABSTRACT_PUBMED_19875080}}		{{ABSTRACT_PUBMED_19875080}}

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

2013-03-06T15:06:06Z

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

← Older revision	Revision as of 15:06, 6 March 2013
(No difference)

OCA at 15:06, 6 March 2013

2013-03-06T15:06:04Z

← Older revision		Revision as of 15:06, 6 March 2013
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	~~{{Seed}}~~
	[[Image:3hlc.png\|left\|200px]]		[[Image:3hlc.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3hlc", 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_3hlc\| PDB=3hlc \| SCENE= }}		{{STRUCTURE_3hlc\| PDB=3hlc \| SCENE= }}

	===Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded===		===Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_19875080}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 19875080 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_19875080}}		{{ABSTRACT_PUBMED_19875080}}

	==About this Structure==		==About this Structure==
	~~3HLC~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA].		[[3hlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA].

			==See Also==
			*[[Simvastatin Synthase\|Simvastatin Synthase]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~19875080~~</ref><references group="xtra"/>		<ref group="xtra">PMID:019875080</ref><references group="xtra"/>
	[[Category: Aspergillus terreus]]		[[Category: Aspergillus terreus]]
	[[Category: Gao, X.]]		[[Category: Gao, X.]]
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	[[Category: Alpha/beta hydrolase fold]]		[[Category: Alpha/beta hydrolase fold]]
	[[Category: Transferase]]		[[Category: Transferase]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 18 18:25:49 2009''~~

OCA at 16:25, 18 November 2009

2009-11-18T16:25:50Z

← Older revision		Revision as of 16:25, 18 November 2009
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
	[[Image:3hlc.~~jpg~~\|left\|200px]]		[[Image:3hlc.png\|left\|200px]]

	<!--		<!--
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	===Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded===		===Simvastatin Synthase (LovD) from Aspergillus terreus, S5 mutant, unliganded===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_19875080}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 19875080 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_19875080}}

	==About this Structure==		==About this Structure==
	3HLC is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA].		3HLC is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HLC OCA].

			==Reference==
			<ref group="xtra">PMID:19875080</ref><references group="xtra"/>
	[[Category: Aspergillus terreus]]		[[Category: Aspergillus terreus]]
	[[Category: Gao, X.]]		[[Category: Gao, X.]]
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	[[Category: Transferase]]		[[Category: Transferase]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Oct 28 13~~:53:31 2009''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 18 18:25:49 2009''