1tdu - Revision history

OCA at 22:12, 7 February 2016

2016-02-07T22:12:55Z

←Older revision		Revision as of 22:12, 7 February 2016
Line 19:		Line 19:
	<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=1tdu ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 05:23, 10 September 2015

2015-09-10T05:23:56Z

←Older revision		Revision as of 05:23, 10 September 2015
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	<StructureSection load='1tdu' size='340' side='right' caption='[[1tdu]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='1tdu' size='340' side='right' caption='[[1tdu]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1tdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Escherichia_coli Escherichia~~ coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TDU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1tdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TDU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=DUR:2-DEOXYURIDINE'>DUR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=DUR:2-DEOXYURIDINE'>DUR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">THYA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 ~~Escherichia~~ coli])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">THYA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </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=1tdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1tdu RCSB], [http://www.ebi.ac.uk/pdbsum/1tdu 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=1tdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdu OCA], [http://pdbe.org/1tdu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tdu RCSB], [http://www.ebi.ac.uk/pdbsum/1tdu PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 29:		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 1tdu" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Escherichia~~ coli]]	+	[[Category: Bacillus coli migula 1895]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Sage, C R]]		[[Category: Sage, C R]]

OCA at 18:33, 24 December 2014

2014-12-24T18:33:46Z

←Older revision		Revision as of 18:33, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1tdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TDU FirstGlance]. <br>		<table><tr><td colspan='2'>[[1tdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TDU FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=DUR:2-DEOXYURIDINE'>DUR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=DUR:2-DEOXYURIDINE'>DUR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">THYA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">THYA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1tdu RCSB], [http://www.ebi.ac.uk/pdbsum/1tdu 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=1tdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1tdu RCSB], [http://www.ebi.ac.uk/pdbsum/1tdu PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TYSY_ECOLI TYSY_ECOLI]] Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 36:		Line 38:
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
-	[[Category: Sage, C R.]]	+	[[Category: Sage, C R]]
-	[[Category: Stout, T J.]]	+	[[Category: Stout, T J]]
-	[[Category: Stroud, R M.]]	+	[[Category: Stroud, R M]]
	[[Category: Methyltransferase]]		[[Category: Methyltransferase]]
	[[Category: Substrate module]]		[[Category: Substrate module]]

OCA at 20:49, 28 September 2014

2014-09-28T20:49:41Z

←Older revision		Revision as of 20:49, 28 September 2014
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-	[[~~Image:~~1tdu.~~png~~\|~~left~~\|200px]]	+	==E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)==
		+	<StructureSection load='1tdu' size='340' side='right' caption='[[1tdu]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1tdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TDU FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=DUR:2-DEOXYURIDINE'>DUR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">THYA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1tdu RCSB], [http://www.ebi.ac.uk/pdbsum/1tdu 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/td/1tdu_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 ==
		+	BACKGROUND: Enzymes have evolved to recognise their target substrates with exquisite selectivity and specificity. Whether fragments of the substrate--perhaps never available to the evolving enzyme--are bound in the same manner as the parent substrate addresses the fundamental basis of specificity. An understanding of the relative contributions of individual portions of ligand molecules to the enzyme-binding interaction may offer considerable insight into the principles of substrate recognition. RESULTS: We report 12 crystal structures of Escherichia coli thymidylate synthase in complexes with available fragments of the substrate (dUMP), both with and without the presence of a cofactor analogue. The structures display considerable fidelity of binding mode and interactions. These complexes reveal several interesting features: the cofactor analogue enhances the localisation of substrate and substrate fragments near the reactive thiol; the ribose moiety reduces local disorder through additional specific enzyme-ligand interactions; the pyrimidine has multiple roles, ranging from stereospecificity to mechanistic competence; and the glycosidic linkage has an important role in the formation of a covalent attachment between substrate and enzyme. CONCLUSIONS: The requirements of ligand-protein binding can be understood in terms of the binding of separate fragments of the ligand. Fragments which are subsystems of the natural substrate for the enzyme confer specific contributions to the binding affinity, orientation or electrostatics of the enzymatic mechanism. This ligand-binding analysis provides a complementary method to the more prevalent approaches utilising site-directed mutagenesis. In addition, these observations suggest a modular approach for rational drug design utilising chemical fragments.

-	~~{{STRUCTURE_1tdu\| PDB=1tdu \| SCENE= }}~~	+	The additivity of substrate fragments in enzyme-ligand binding.,Stout TJ, Sage CR, Stroud RM Structure. 1998 Jul 15;6(7):839-48. PMID:9687366<ref>PMID:9687366</ref>

-	~~===E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_9687366}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1tdu]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Escherichia_coli Escherichia coli]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA].~~	+

	==See Also==		==See Also==
	*[[Thymidylate synthase\|Thymidylate synthase]]		*[[Thymidylate synthase\|Thymidylate synthase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:009687366<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]

OCA at 08:00, 20 October 2012

2012-10-20T08:00:38Z

←Older revision		Revision as of 08:00, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1tdu]] is a 2 chain structure ~~of [[Thymidylate synthase]]~~ with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA].	+	[[1tdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA].

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

OCA: Protected "1tdu" [edit=sysop:move=sysop]

2012-07-25T18:09:57Z

Protected "1tdu" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:09, 25 July 2012

OCA at 18:09, 25 July 2012

2012-07-25T18:09:56Z

←Older revision		Revision as of 18:09, 25 July 2012
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-	{{Seed}}
	[[Image:1tdu.png\|left\|200px]]		[[Image:1tdu.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1tdu", creates the "Structure Box" on the page.
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-	or leave the SCENE parameter empty for the default display.
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	{{STRUCTURE_1tdu\| PDB=1tdu \| SCENE= }}		{{STRUCTURE_1tdu\| PDB=1tdu \| SCENE= }}

	===E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)===		===E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_9687366}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 9687366 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_9687366}}		{{ABSTRACT_PUBMED_9687366}}

	==About this Structure==		==About this Structure==
-	~~1TDU~~ is a 2 ~~chains~~ structure of ~~sequences~~ from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA].	+	[[1tdu]] is a 2 chain structure of [[Thymidylate synthase]] with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA].
		+
		+	==See Also==
		+	*[[Thymidylate synthase\|Thymidylate synthase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~9687366~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:009687366</ref><references group="xtra"/>
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
Line 29:		Line 20:
	[[Category: Stout, T J.]]		[[Category: Stout, T J.]]
	[[Category: Stroud, R M.]]		[[Category: Stroud, R M.]]
		+	[[Category: Methyltransferase]]
	[[Category: Substrate module]]		[[Category: Substrate module]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 16:50:27 2009''

OCA at 14:50, 16 February 2009

2009-02-16T14:50:27Z

←Older revision		Revision as of 14:50, 16 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	1TDU is a ~~[[Single protein]]~~ structure of ~~sequence~~ from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA].	+	1TDU is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDU OCA].

	==Reference==		==Reference==
-	~~The additivity of substrate fragments in enzyme-ligand binding., Stout TJ, Sage CR, Stroud RM, Structure. 1998 Jul 15;6(7):839-48.~~ PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/9687366 9687366]~~	+	<ref group="xtra">PMID:9687366</ref><references group="xtra"/>
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
-	[[Category: Single protein]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Sage, C R.]]		[[Category: Sage, C R.]]
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	[[Category: Substrate module]]		[[Category: Substrate module]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun Jul 27 20~~:06:~~08 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 16:50:27 2009''

OCA at 17:06, 27 July 2008

2008-07-27T17:06:14Z

←Older revision		Revision as of 17:06, 27 July 2008
Line 1:		Line 1:
-	[[Image:1tdu.~~jpg~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:1tdu.png\|left\|200px]]

	<!--		<!--
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	{{STRUCTURE_1tdu\| PDB=1tdu \| SCENE= }}		{{STRUCTURE_1tdu\| PDB=1tdu \| SCENE= }}

-	~~'''~~E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)~~'''~~	+	===E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)===


-	~~==Overview==~~	+	<!--
-	~~BACKGROUND: Enzymes have evolved to recognise their target substrates with exquisite selectivity and specificity. Whether fragments of the substrate~~--~~perhaps never available to the evolving enzyme--are bound in the same manner as the parent substrate addresses the fundamental basis of specificity. An understanding of~~ the ~~relative contributions of individual portions of ligand molecules~~ to the enzyme-binding interaction may offer considerable insight into the principles of substrate recognition. RESULTS: We report 12 crystal structures of Escherichia coli thymidylate synthase in complexes with available fragments of the substrate (~~dUMP), both with and without the presence of a cofactor analogue. The structures display considerable fidelity of binding mode and interactions. These complexes reveal several interesting features~~: the cofactor analogue enhances the localisation of substrate and substrate fragments near the reactive thiol; the ribose moiety reduces local disorder through additional specific enzyme-ligand interactions; the pyrimidine has multiple roles, ranging from stereospecificity to mechanistic competence; and the glycosidic linkage has an important role in the formation of a covalent attachment between substrate and enzyme. ~~CONCLUSIONS: The requirements of ligand-protein binding can be understood in terms of the binding of separate fragments of the ligand~~. ~~Fragments which are subsystems of the natural substrate for the enzyme confer specific contributions to the binding affinity~~, ~~orientation or electrostatics of~~ the ~~enzymatic mechanism~~. ~~This ligand~~-~~binding analysis provides a complementary method to the more prevalent approaches utilising site~~-~~directed mutagenesis. In addition, these observations suggest a modular approach for rational drug design utilising chemical fragments.~~	+	The line below this paragraph, {{ABSTRACT_PUBMED_9687366}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 9687366 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_9687366}}

	==About this Structure==		==About this Structure==
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	[[Category: Stroud, R M.]]		[[Category: Stroud, R M.]]
	[[Category: Substrate module]]		[[Category: Substrate module]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May 3 09~~:50:00 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:06:08 2008''

OCA at 06:50, 3 May 2008

2008-05-03T06:50:03Z

←Older revision		Revision as of 06:50, 3 May 2008
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	[[Image:1tdu.jpg\|left\|200px]]		[[Image:1tdu.jpg\|left\|200px]]

-	~~{{Structure~~	+	<!--
-	~~\|PDB= 1tdu \|SIZE=350\|CAPTION=~~ <~~scene name='initialview01'>1tdu</scene>, resolution 2.10Å~~	+	The line below this paragraph, containing "STRUCTURE_1tdu", creates the "Structure Box" on the page.
-	~~\|SITE= <scene name='pdbsite=ACT:Active+Site+Reactive+Thiol'>ACT</scene>~~	+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	~~\|LIGAND= <scene name='pdbligand=CB3:10~~-~~PROPARGYL~~-5,~~8-DIDEAZAFOLIC+ACID'>CB3</scene>~~, ~~<scene name='pdbligand=DUR:2'-DEOXYURIDINE'>DUR</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>~~	+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	~~\|ACTIVITY= <span class='plainlinks'>[http://en~~.~~wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span>~~	+	or leave the SCENE parameter empty for the default display.
-	~~\|GENE= THYA~~ (~~[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]~~)	+	-->
-	~~\|DOMAIN=~~	+	{{STRUCTURE_1tdu\| PDB=1tdu \| SCENE= }}
-	~~\|RELATEDENTRY=~~	+
-	~~\|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca~~-~~docs/fgij/fg.htm?mol=1tdu FirstGlance], [http://oca.weizmann.ac.il/oca~~-~~bin/ocaids?id~~=1tdu ~~OCA], [http://www.ebi.ac.uk/pdbsum/1tdu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId~~=~~1tdu RCSB]</span>~~	+
-	}}	+

	'''E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)'''		'''E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE (DURD)'''
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	[[Category: Stout, T J.]]		[[Category: Stout, T J.]]
	[[Category: Stroud, R M.]]		[[Category: Stroud, R M.]]
-	[[Category: ~~substrate~~ module]]	+	[[Category: Substrate module]]
-	~~[[Category: transferase (methyltransferase)]]~~	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:50:00 2008''
-		+
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun Mar 30 23~~:54:43 2008''	+