3hrq - Revision history

OCA at 10:01, 21 February 2024

OCA — Wed, 21 Feb 2024 10:01:21 GMT

←Older revision		Revision as of 10:01, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3hrq' size='340' side='right'caption='[[3hrq]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3hrq' size='340' side='right'caption='[[3hrq]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hrq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Asppa Asppa~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HRQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hrq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HRQ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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]] 1.8Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style~~=~~'overflow: auto; max-height: 3em;'~~>~~[[3hrr\|3hrr]]~~<~~/div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">PksA, pksL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 ASPPA])~~</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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [https://pdbe.org/3hrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [https://www.ebi.ac.uk/pdbsum/3hrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hrq 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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [https://pdbe.org/3hrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [https://www.ebi.ac.uk/pdbsum/3hrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hrq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/~~PKSL1_ASPPA PKSL1_ASPPA~~]~~] Combines~~ a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor norsolorinic acid ~~anthrone~~ (~~noranthrone~~) ~~in the aflatoxin biosynthesis pathway~~. The hexanoyl starter unit is ~~provided~~ to the ~~acyl~~-~~carrier protein~~ (~~ACP~~) ~~domain~~ by a ~~dedicated fungal fatty acid~~ synthase.<ref>PMID:~~15006741~~</ref> <ref>PMID:18403714</ref>	+	[https://www.uniprot.org/uniprot/AFLC_ASPPU AFLC_ASPPU] Norsolorinic acid synthase; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins (PubMed:7592391, PubMed:15094053, PubMed:7565588, PubMed:15006741, PubMed:17086560, PubMed:18403714). The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741). Within the aflatoxin pathway, the norsolorinic acid synthase aflC combines a hexanoyl starter unit provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase aflA/aflB, and 7 malonyl-CoA extender units to synthesize the precursor norsolorinic acid (NOR) (PubMed:17086560, PubMed:18403714). The biosynthesis of aflatoxins begins with the norsolorinic acid synthase aflC that combines a hexanoyl starter unit produced by the fatty acid synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the precursor NOR. The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively. Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741).<ref>PMID:17086560</ref> <ref>PMID:18403714</ref> <ref>PMID:7565588</ref> <ref>PMID:7592391</ref> <ref>PMID:15006741</ref> <ref>PMID:15094053</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=3hrq 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=3hrq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Polyketides are a class of natural products with diverse structures and biological activities. The structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs) results from regiospecific cyclizations of reactive poly-beta-keto intermediates. How poly-beta-keto species are synthesized and stabilized, how their chain lengths are determined, and, in particular, how specific cyclization patterns are controlled have been largely inaccessible and functionally unknown until recently. A product template (PT) domain is responsible for controlling specific aldol cyclization and aromatization of these mature polyketide precursors, but the mechanistic basis is unknown. Here we present the 1.8 A crystal structure and mutational studies of a dissected PT monodomain from PksA, the NR-PKS that initiates the biosynthesis of the potent hepatocarcinogen aflatoxin B(1) in Aspergillus parasiticus. Despite having minimal sequence similarity to known enzymes, the structure displays a distinct 'double hot dog' (DHD) fold. Co-crystal structures with palmitate or a bicyclic substrate mimic illustrate that PT can bind both linear and bicyclic polyketides. Docking and mutagenesis studies reveal residues important for substrate binding and catalysis, and identify a phosphopantetheine localization channel and a deep two-part interior binding pocket and reaction chamber. Sequence similarity and extensive conservation of active site residues in PT domains suggest that the mechanistic insights gleaned from these studies will prove general for this class of IPKSs, and lay a foundation for defining the molecular rules controlling NR-PKS cyclization specificity.
-
-	Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization.,Crawford JM, Korman TP, Labonte JW, Vagstad AL, Hill EA, Kamari-Bidkorpeh O, Tsai SC, Townsend CA Nature. 2009 Oct 22;461(7267):1139-43. PMID:19847268<ref>PMID:19847268</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3hrq" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Asppa~~]]	+	[[Category: Aspergillus parasiticus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Korman~~, T P~~]]	+	[[Category: Korman TP]]
-	[[Category: Tsai~~, S C]]~~	+	[[Category: Tsai SC]]
-	~~[[Category: Acyltransferase]]~~	+
-	~~[[Category: Aflatoxin]]~~	+
-	~~[[Category: Biosynthetic protein]]~~	+
-	~~[[Category: Hot-dog fold]]~~	+
-	~~[[Category: Iterative type i pk]]~~	+
-	~~[[Category: Multifunctional enzyme]]~~	+
-	~~[[Category: Norsolorinic acid]]~~	+
-	~~[[Category: Phosphopantetheine]]~~	+
-	~~[[Category: Pksa]]~~	+
-	~~[[Category: Polyketide synthase]]~~	+
-	~~[[Category: Product template domain~~]]	+

OCA at 11:55, 30 March 2022

OCA — Wed, 30 Mar 2022 11:55:49 GMT

←Older revision		Revision as of 11:55, 30 March 2022
Line 1:		Line 1:

	==The Product Template Domain from PksA with palmitate bound==		==The Product Template Domain from PksA with palmitate bound==
-	<StructureSection load='3hrq' size='340' side='right' caption='[[3hrq]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='3hrq' size='340' side='right'caption='[[3hrq]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hrq]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Asppa Asppa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3HRQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hrq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Asppa Asppa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HRQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hrr\|3hrr]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3hrr\|3hrr]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PksA, pksL1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 ASPPA])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PksA, pksL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 ASPPA])</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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [~~http~~://pdbe.org/3hrq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3hrq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3hrq 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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [https://pdbe.org/3hrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [https://www.ebi.ac.uk/pdbsum/3hrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hrq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PKSL1_ASPPA PKSL1_ASPPA]] Combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor norsolorinic acid anthrone (noranthrone) in the aflatoxin biosynthesis pathway. The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by a dedicated fungal fatty acid synthase.<ref>PMID:15006741</ref> <ref>PMID:18403714</ref>	+	[[https://www.uniprot.org/uniprot/PKSL1_ASPPA PKSL1_ASPPA]] Combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor norsolorinic acid anthrone (noranthrone) in the aflatoxin biosynthesis pathway. The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by a dedicated fungal fatty acid synthase.<ref>PMID:15006741</ref> <ref>PMID:18403714</ref>
	== 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/hr/3hrq_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/3hrq_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 35:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Asppa]]		[[Category: Asppa]]
		+	[[Category: Large Structures]]
	[[Category: Korman, T P]]		[[Category: Korman, T P]]
	[[Category: Tsai, S C]]		[[Category: Tsai, S C]]

OCA at 08:44, 5 August 2016

OCA — Fri, 05 Aug 2016 08:44:57 GMT

←Older revision		Revision as of 08:44, 5 August 2016
Line 1:		Line 1:
		+
	==The Product Template Domain from PksA with palmitate bound==		==The Product Template Domain from PksA with palmitate bound==
	<StructureSection load='3hrq' size='340' side='right' caption='[[3hrq]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3hrq' size='340' side='right' caption='[[3hrq]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hrq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Aspergillus_parasiticus Aspergillus parasiticus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HRQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hrq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Asppa Asppa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HRQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hrr\|3hrr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hrr\|3hrr]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PksA, pksL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 ~~Aspergillus parasiticus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PksA, pksL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 ASPPA])</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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [http://www.ebi.ac.uk/pdbsum/3hrq 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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [http://pdbe.org/3hrq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [http://www.ebi.ac.uk/pdbsum/3hrq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hrq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	<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=3hrq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 28:		Line 29:
	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 3hrq" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Aspergillus parasiticus~~]]	+	[[Category: Asppa]]
	[[Category: Korman, T P]]		[[Category: Korman, T P]]
	[[Category: Tsai, S C]]		[[Category: Tsai, S C]]

OCA at 17:23, 25 December 2014

OCA — Thu, 25 Dec 2014 17:23:18 GMT

←Older revision		Revision as of 17:23, 25 December 2014
Line 8:		Line 8:
	<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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [http://www.ebi.ac.uk/pdbsum/3hrq 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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [http://www.ebi.ac.uk/pdbsum/3hrq PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PKSL1_ASPPA PKSL1_ASPPA]] Combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor norsolorinic acid anthrone (noranthrone) in the aflatoxin biosynthesis pathway. The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by a dedicated fungal fatty acid synthase.<ref>PMID:15006741</ref> <ref>PMID:18403714</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 06:14, 18 December 2014

OCA — Thu, 18 Dec 2014 06:14:30 GMT

←Older revision		Revision as of 06:14, 18 December 2014
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-	~~{{STRUCTURE_3hrq\| PDB=3hrq \| SCENE= }}~~	+	==The Product Template Domain from PksA with palmitate bound==
-	===The Product Template Domain from PksA with palmitate bound===	+	<StructureSection load='3hrq' size='340' side='right' caption='[[3hrq]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19847268}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3hrq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HRQ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hrr\|3hrr]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PksA, pksL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 Aspergillus parasiticus])</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=3hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hrq RCSB], [http://www.ebi.ac.uk/pdbsum/3hrq 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/hr/3hrq_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 ==
		+	Polyketides are a class of natural products with diverse structures and biological activities. The structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs) results from regiospecific cyclizations of reactive poly-beta-keto intermediates. How poly-beta-keto species are synthesized and stabilized, how their chain lengths are determined, and, in particular, how specific cyclization patterns are controlled have been largely inaccessible and functionally unknown until recently. A product template (PT) domain is responsible for controlling specific aldol cyclization and aromatization of these mature polyketide precursors, but the mechanistic basis is unknown. Here we present the 1.8 A crystal structure and mutational studies of a dissected PT monodomain from PksA, the NR-PKS that initiates the biosynthesis of the potent hepatocarcinogen aflatoxin B(1) in Aspergillus parasiticus. Despite having minimal sequence similarity to known enzymes, the structure displays a distinct 'double hot dog' (DHD) fold. Co-crystal structures with palmitate or a bicyclic substrate mimic illustrate that PT can bind both linear and bicyclic polyketides. Docking and mutagenesis studies reveal residues important for substrate binding and catalysis, and identify a phosphopantetheine localization channel and a deep two-part interior binding pocket and reaction chamber. Sequence similarity and extensive conservation of active site residues in PT domains suggest that the mechanistic insights gleaned from these studies will prove general for this class of IPKSs, and lay a foundation for defining the molecular rules controlling NR-PKS cyclization specificity.

-	~~==About this Structure==~~	+	Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization.,Crawford JM, Korman TP, Labonte JW, Vagstad AL, Hill EA, Kamari-Bidkorpeh O, Tsai SC, Townsend CA Nature. 2009 Oct 22;461(7267):1139-43. PMID:19847268<ref>PMID:19847268</ref>
-	~~[[3hrq]] is a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	<~~ref group="xtra">PMID:019847268<~~/~~ref~~><~~references group="xtra"~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Aspergillus parasiticus]]		[[Category: Aspergillus parasiticus]]
-	[[Category: Korman, T P.]]	+	[[Category: Korman, T P]]
-	[[Category: Tsai, S C.]]	+	[[Category: Tsai, S C]]
	[[Category: Acyltransferase]]		[[Category: Acyltransferase]]
	[[Category: Aflatoxin]]		[[Category: Aflatoxin]]

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

OCA — Wed, 13 Mar 2013 10:50:11 GMT

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

←Older revision

Revision as of 10:50, 13 March 2013

OCA at 10:50, 13 March 2013

OCA — Wed, 13 Mar 2013 10:50:06 GMT

←Older revision		Revision as of 10:50, 13 March 2013
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-	{{Seed}}
-	[[Image:3hrq.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3hrq", 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_3hrq\| PDB=3hrq \| SCENE= }}		{{STRUCTURE_3hrq\| PDB=3hrq \| SCENE= }}
-
	===The Product Template Domain from PksA with palmitate bound===		===The Product Template Domain from PksA with palmitate bound===
-
-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19847268}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19847268 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19847268}}		{{ABSTRACT_PUBMED_19847268}}

	==About this Structure==		==About this Structure==
-	~~3HRQ~~ is a 2 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA].	+	[[3hrq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19847268~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019847268</ref><references group="xtra"/>
	[[Category: Aspergillus parasiticus]]		[[Category: Aspergillus parasiticus]]
	[[Category: Korman, T P.]]		[[Category: Korman, T P.]]
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	[[Category: Polyketide synthase]]		[[Category: Polyketide synthase]]
	[[Category: Product template domain]]		[[Category: Product template domain]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 30 14:19:26 2009''

OCA at 12:19, 30 December 2009

OCA — Wed, 30 Dec 2009 12:19:27 GMT

←Older revision		Revision as of 12:19, 30 December 2009
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	{{Seed}}		{{Seed}}
-	[[Image:3hrq.~~jpg~~\|left\|200px]]	+	[[Image:3hrq.png\|left\|200px]]

	<!--		<!--
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	===The Product Template Domain from PksA with palmitate bound===		===The Product Template Domain from PksA with palmitate bound===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19847268}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19847268 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19847268}}

	==About this Structure==		==About this Structure==
	3HRQ is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA].		3HRQ is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19847268</ref><references group="xtra"/>
	[[Category: Aspergillus parasiticus]]		[[Category: Aspergillus parasiticus]]
	[[Category: Korman, T P.]]		[[Category: Korman, T P.]]
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	[[Category: Product template domain]]		[[Category: Product template domain]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Oct 21 10~~:37:27 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 30 14:19:26 2009''

OCA at 08:37, 21 October 2009

OCA — Wed, 21 Oct 2009 08:37:29 GMT

←Older revision		Revision as of 08:37, 21 October 2009
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-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3hrq.jpg\|left\|200px]]

-	The ~~entry 3hrq~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3hrq", 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_3hrq\| PDB=3hrq \| SCENE= }}

-	~~Authors: Korman, T.P., Tsai, S.-C.~~	+	===The Product Template Domain from PksA with palmitate bound===

-	Description: The Product Template Domain from PksA with palmitate bound

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Aug 12 12~~:23:48 2009''	+	==About this Structure==
		+	3HRQ is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRQ OCA].
		+	[[Category: Aspergillus parasiticus]]
		+	[[Category: Korman, T P.]]
		+	[[Category: Tsai, S C.]]
		+	[[Category: Acyltransferase]]
		+	[[Category: Aflatoxin]]
		+	[[Category: Biosynthetic protein]]
		+	[[Category: Hot-dog fold]]
		+	[[Category: Iterative type i pk]]
		+	[[Category: Multifunctional enzyme]]
		+	[[Category: Norsolorinic acid]]
		+	[[Category: Phosphopantetheine]]
		+	[[Category: Pksa]]
		+	[[Category: Polyketide synthase]]
		+	[[Category: Product template domain]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 21 10:37:27 2009''

OCA at 09:23, 12 August 2009

OCA — Wed, 12 Aug 2009 09:23:49 GMT

←Older revision		Revision as of 09:23, 12 August 2009
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3hrq is ON HOLD	+	The entry 3hrq is ON HOLD until Paper Publication

	Authors: Korman, T.P., Tsai, S.-C.		Authors: Korman, T.P., Tsai, S.-C.
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	Description: The Product Template Domain from PksA with palmitate bound		Description: The Product Template Domain from PksA with palmitate bound

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Jun 25 08~~:11:37 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 12 12:23:48 2009''