2res - Revision history

OCA at 09:21, 21 February 2024

OCA — Wed, 21 Feb 2024 09:21:57 GMT

←Older revision		Revision as of 09:21, 21 February 2024
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	<StructureSection load='2res' size='340' side='right'caption='[[2res]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='2res' size='340' side='right'caption='[[2res]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"actinomyces_glaucescens"_preobrazhenskaya_in_gauze_et_al._1957 "actinomyces~~ glaucescens~~" preobrazhenskaya in gauze et al. 1957~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RES FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RES FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[2rer\|2rer]]</div></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]] 2.2Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">tcmN ([https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=1907 "Actinomyces glaucescens" Preobrazhenskaya in Gauze et al. 1957])~~</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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [https://pdbe.org/2res PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [https://www.ebi.ac.uk/pdbsum/2res PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2res 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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [https://pdbe.org/2res PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [https://www.ebi.ac.uk/pdbsum/2res PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2res ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TCMN_STRGA TCMN_STRGA]] The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2.	+	[https://www.uniprot.org/uniprot/TCMN_STRGA TCMN_STRGA] The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 19:
	</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=2res 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=2res 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 highly diverse chemical structures and pharmaceutical activities. Polyketide cyclization, promoted by the aromatase/cyclase (ARO/CYC), helps diversify aromatic polyketides. How the ARO/CYC promotes highly specific cyclization is not well understood because of the lack of a first-ring ARO/CYC structure. The 1.9 A crystal structure of Tcm ARO/CYC reveals that the enzyme belongs to the Bet v1-like superfamily (or STAR domain family) with a helix-grip fold, and contains a highly conserved interior pocket. Docking, mutagenesis, and an in vivo assay show that the size, shape, and composition of the pocket are important to orient and specifically fold the polyketide chain for C9-C14 first-ring and C7-C16 second-ring cyclizations. Two pocket residues, R69 and Y35, were found to be essential for promoting first- and second-ring cyclization specificity. Different pocket residue mutations affected the polyketide product distribution. A mechanism is proposed based on the structure-mutation-docking results. These results strongly suggest that the regiospecific cyclizations of the first two rings and subsequent aromatizations take place in the interior pocket. The chemical insights gleaned from this work pave the foundation toward defining the molecular rules for the ARO/CYC cyclization specificity, whose rational control will be important for future endeavors in the engineered biosynthesis of novel anticancer and antibiotic aromatic polyketides.
-
-	Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides.,Ames BD, Korman TP, Zhang W, Smith P, Vu T, Tang Y, Tsai SC Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5349-54. Epub 2008 Apr 3. PMID:18388203<ref>PMID:18388203</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2res" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Actinomyces glaucescens preobrazhenskaya in gauze et al. 1957]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Ames, B D~~]]	+	[[Category: Streptomyces glaucescens]]
-	[[Category: ~~Tsai, S C~~]]	+	[[Category: Ames BD]]
-	[[Category: ~~Antibiotic biosynthesis]]~~	+	[[Category: Tsai SC]]
-	~~[[Category: Aromatase]]~~	+
-	~~[[Category: Biosynthetic protein]]~~	+
-	~~[[Category: Cyclase]]~~	+
-	~~[[Category: Dehydratase]]~~	+
-	~~[[Category: Helix-grip]]~~	+
-	~~[[Category: Lyase]]~~	+
-	~~[[Category: Methyltransferase]]~~	+
-	~~[[Category: Multifunctional enzyme]]~~	+
-	~~[[Category: Polyketide]]~~	+
-	~~[[Category: Tetracenomycin]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 04:23, 2 July 2021

OCA — Fri, 02 Jul 2021 04:23:12 GMT

←Older revision		Revision as of 04:23, 2 July 2021
Line 1:		Line 1:

	==Tetracenomycin ARO/CYC mutant R69A==		==Tetracenomycin ARO/CYC mutant R69A==
-	<StructureSection load='2res' size='340' side='right' caption='[[2res]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='2res' size='340' side='right'caption='[[2res]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"actinomyces_glaucescens"_preobrazhenskaya_in_gauze_et_al._1957 "actinomyces glaucescens" preobrazhenskaya in gauze et al. 1957]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2RES FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_glaucescens"_preobrazhenskaya_in_gauze_et_al._1957 "actinomyces glaucescens" preobrazhenskaya in gauze et al. 1957]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RES FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2rer\|2rer]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2rer\|2rer]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">tcmN ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 "Actinomyces glaucescens" Preobrazhenskaya in Gauze et al. 1957])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">tcmN ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 "Actinomyces glaucescens" Preobrazhenskaya in Gauze et al. 1957])</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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [~~http~~://pdbe.org/2res PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2res PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2res 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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [https://pdbe.org/2res PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [https://www.ebi.ac.uk/pdbsum/2res PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2res ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/TCMN_STRGA TCMN_STRGA]] The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2.	+	[[https://www.uniprot.org/uniprot/TCMN_STRGA TCMN_STRGA]] The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 34:
	</StructureSection>		</StructureSection>
	[[Category: Actinomyces glaucescens preobrazhenskaya in gauze et al. 1957]]		[[Category: Actinomyces glaucescens preobrazhenskaya in gauze et al. 1957]]
		+	[[Category: Large Structures]]
	[[Category: Ames, B D]]		[[Category: Ames, B D]]
	[[Category: Tsai, S C]]		[[Category: Tsai, S C]]

OCA at 11:27, 5 September 2018

OCA — Wed, 05 Sep 2018 11:27:33 GMT

←Older revision		Revision as of 11:27, 5 September 2018
Line 14:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/re/2res_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/re/2res_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>

OCA at 06:21, 5 August 2016

OCA — Fri, 05 Aug 2016 06:21:27 GMT

←Older revision		Revision as of 06:21, 5 August 2016
Line 1:		Line 1:
		+
	==Tetracenomycin ARO/CYC mutant R69A==		==Tetracenomycin ARO/CYC mutant R69A==
	<StructureSection load='2res' size='340' side='right' caption='[[2res]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='2res' size='340' side='right' caption='[[2res]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Streptomyces_glaucescens Streptomyces~~ glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RES FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_glaucescens"_preobrazhenskaya_in_gauze_et_al._1957 "actinomyces glaucescens" preobrazhenskaya in gauze et al. 1957]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RES FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2rer\|2rer]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2rer\|2rer]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">tcmN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 ~~Streptomyces~~ glaucescens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">tcmN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 "Actinomyces glaucescens" Preobrazhenskaya in Gauze et al. 1957])</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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [http://www.ebi.ac.uk/pdbsum/2res 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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [http://pdbe.org/2res PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [http://www.ebi.ac.uk/pdbsum/2res PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2res ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	<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=2res ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 27:		Line 28:
	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 2res" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Streptomyces~~ glaucescens]]	+	[[Category: Actinomyces glaucescens preobrazhenskaya in gauze et al. 1957]]
	[[Category: Ames, B D]]		[[Category: Ames, B D]]
	[[Category: Tsai, S C]]		[[Category: Tsai, S C]]

OCA at 16:28, 25 December 2014

OCA — Thu, 25 Dec 2014 16:28:50 GMT

←Older revision		Revision as of 16:28, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RES FirstGlance]. <br>		<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RES FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2rer\|2rer]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2rer\|2rer]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">tcmN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 Streptomyces glaucescens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">tcmN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 Streptomyces glaucescens])</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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [http://www.ebi.ac.uk/pdbsum/2res 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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [http://www.ebi.ac.uk/pdbsum/2res PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TCMN_STRGA TCMN_STRGA]] The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 30:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: Streptomyces glaucescens]]		[[Category: Streptomyces glaucescens]]
-	[[Category: Ames, B D.]]	+	[[Category: Ames, B D]]
-	[[Category: Tsai, S C.]]	+	[[Category: Tsai, S C]]
	[[Category: Antibiotic biosynthesis]]		[[Category: Antibiotic biosynthesis]]
	[[Category: Aromatase]]		[[Category: Aromatase]]

OCA at 19:39, 30 September 2014

OCA — Tue, 30 Sep 2014 19:39:30 GMT

←Older revision		Revision as of 19:39, 30 September 2014
Line 1:		Line 1:
-	[[~~Image:~~2res.~~png~~\|~~left~~\|200px]]	+	==Tetracenomycin ARO/CYC mutant R69A==
		+	<StructureSection load='2res' size='340' side='right' caption='[[2res]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2res]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RES FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2rer\|2rer]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">tcmN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 Streptomyces glaucescens])</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=2res FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2res OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2res RCSB], [http://www.ebi.ac.uk/pdbsum/2res 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/re/2res_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 highly diverse chemical structures and pharmaceutical activities. Polyketide cyclization, promoted by the aromatase/cyclase (ARO/CYC), helps diversify aromatic polyketides. How the ARO/CYC promotes highly specific cyclization is not well understood because of the lack of a first-ring ARO/CYC structure. The 1.9 A crystal structure of Tcm ARO/CYC reveals that the enzyme belongs to the Bet v1-like superfamily (or STAR domain family) with a helix-grip fold, and contains a highly conserved interior pocket. Docking, mutagenesis, and an in vivo assay show that the size, shape, and composition of the pocket are important to orient and specifically fold the polyketide chain for C9-C14 first-ring and C7-C16 second-ring cyclizations. Two pocket residues, R69 and Y35, were found to be essential for promoting first- and second-ring cyclization specificity. Different pocket residue mutations affected the polyketide product distribution. A mechanism is proposed based on the structure-mutation-docking results. These results strongly suggest that the regiospecific cyclizations of the first two rings and subsequent aromatizations take place in the interior pocket. The chemical insights gleaned from this work pave the foundation toward defining the molecular rules for the ARO/CYC cyclization specificity, whose rational control will be important for future endeavors in the engineered biosynthesis of novel anticancer and antibiotic aromatic polyketides.

-	~~{{STRUCTURE_2res\| PDB=2res \| SCENE= }}~~	+	Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides.,Ames BD, Korman TP, Zhang W, Smith P, Vu T, Tang Y, Tsai SC Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5349-54. Epub 2008 Apr 3. PMID:18388203<ref>PMID:18388203</ref>

-	~~===Tetracenomycin ARO~~/~~CYC mutant R69A===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_18388203}}~~	+	== References ==
-		+	<references/>
-	~~==About this Structure==~~	+	__TOC__
-	~~[[2res]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA].~~	+	</StructureSection>
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:018388203<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Streptomyces glaucescens]]		[[Category: Streptomyces glaucescens]]
	[[Category: Ames, B D.]]		[[Category: Ames, B D.]]

OCA: Protected "2res" [edit=sysop:move=sysop]

OCA — Mon, 07 Jan 2013 19:45:02 GMT

Protected "2res" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:45, 7 January 2013

OCA at 19:44, 7 January 2013

OCA — Mon, 07 Jan 2013 19:44:59 GMT

←Older revision		Revision as of 19:44, 7 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2res.png\|left\|200px]]		[[Image:2res.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2res", 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_2res\| PDB=2res \| SCENE= }}		{{STRUCTURE_2res\| PDB=2res \| SCENE= }}

	===Tetracenomycin ARO/CYC mutant R69A===		===Tetracenomycin ARO/CYC mutant R69A===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_18388203}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 18388203 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_18388203}}		{{ABSTRACT_PUBMED_18388203}}

	==About this Structure==		==About this Structure==
-	~~2RES~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA].	+	[[2res]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~18388203~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018388203</ref><references group="xtra"/>
	[[Category: Streptomyces glaucescens]]		[[Category: Streptomyces glaucescens]]
	[[Category: Ames, B D.]]		[[Category: Ames, B D.]]
Line 39:		Line 27:
	[[Category: Tetracenomycin]]		[[Category: Tetracenomycin]]
	[[Category: Transferase]]		[[Category: Transferase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 21:46:37 2009''

OCA at 19:46, 17 February 2009

OCA — Tue, 17 Feb 2009 19:46:38 GMT

←Older revision		Revision as of 19:46, 17 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	2RES is a ~~[[Single protein]]~~ structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA].	+	2RES is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RES OCA].

	==Reference==		==Reference==
-	Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides., Ames BD, Korman TP, Zhang W, Smith P, Vu T, Tang Y, Tsai SC, Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5349-54. Epub 2008 Apr 3. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/18388203 18388203]~~	+	<ref group="xtra">PMID:18388203</ref><references group="xtra"/>
-	~~[[Category: Single protein]]~~	+
	[[Category: Streptomyces glaucescens]]		[[Category: Streptomyces glaucescens]]
	[[Category: Ames, B D.]]		[[Category: Ames, B D.]]
Line 41:		Line 40:
	[[Category: Transferase]]		[[Category: Transferase]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue ~~Jul 29 05~~:57:~~14 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 21:46:37 2009''

OCA at 02:57, 29 July 2008

OCA — Tue, 29 Jul 2008 02:57:19 GMT

←Older revision		Revision as of 02:57, 29 July 2008
Line 1:		Line 1:
-	[[Image:2res.~~jpg~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:2res.png\|left\|200px]]

	<!--		<!--
Line 9:		Line 10:
	{{STRUCTURE_2res\| PDB=2res \| SCENE= }}		{{STRUCTURE_2res\| PDB=2res \| SCENE= }}

-	~~'''~~Tetracenomycin ARO/CYC mutant R69A~~'''~~	+	===Tetracenomycin ARO/CYC mutant R69A===


-	~~==Overview==~~	+	<!--
-	~~Polyketides are a class of natural products with highly diverse chemical structures and pharmaceutical activities. Polyketide cyclization~~, ~~promoted by~~ the ~~aromatase/cyclase~~ (~~ARO~~/~~CYC), helps diversify aromatic polyketides. How the ARO~~/~~CYC promotes highly specific cyclization is not well understood because of the lack of a first-ring ARO/CYC structure~~. ~~The 1~~.~~9 A crystal structure of Tcm ARO/CYC reveals that the enzyme belongs to the Bet v1-like superfamily (or STAR domain family~~) ~~with a helix-grip fold~~, ~~and contains a highly conserved interior pocket. Docking, mutagenesis, and an in vivo assay show that~~ the ~~size, shape, and composition of the pocket are important to orient and specifically fold the polyketide chain for C9-C14 first-ring and C7-C16 second-ring cyclizations~~. ~~Two pocket residues, R69 and Y35, were found to be essential for promoting first~~- ~~and second~~-ring cyclization specificity. Different pocket residue mutations affected the polyketide product distribution. A mechanism is proposed based on the structure-mutation-docking results. These results strongly suggest that the regiospecific cyclizations of the first two rings and subsequent aromatizations take place in the interior pocket. The chemical insights gleaned from this work pave the foundation toward defining the molecular rules for the ARO/CYC cyclization specificity, whose rational control will be important for future endeavors in the engineered biosynthesis of novel anticancer and antibiotic aromatic polyketides.	+	The line below this paragraph, {{ABSTRACT_PUBMED_18388203}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 18388203 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_18388203}}

	==About this Structure==		==About this Structure==
Line 36:		Line 40:
	[[Category: Tetracenomycin]]		[[Category: Tetracenomycin]]
	[[Category: Transferase]]		[[Category: Transferase]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Apr 24 09~~:42:18 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:57:14 2008''