1tsn

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{{Seed}}
 
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[[Image:1tsn.png|left|200px]]
 
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==THYMIDYLATE SYNTHASE TERNARY COMPLEX WITH FDUMP AND METHYLENETETRAHYDROFOLATE==
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The line below this paragraph, containing "STRUCTURE_1tsn", creates the "Structure Box" on the page.
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<StructureSection load='1tsn' size='340' side='right'caption='[[1tsn]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1tsn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TSN FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C2F:5-METHYL-5,6,7,8-TETRAHYDROFOLIC+ACID'>C2F</scene>, <scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</scene></td></tr>
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{{STRUCTURE_1tsn| PDB=1tsn | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tsn OCA], [https://pdbe.org/1tsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tsn RCSB], [https://www.ebi.ac.uk/pdbsum/1tsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tsn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ts/1tsn_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1tsn ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Two crystal structures for E. coli thymidylate synthase (TS) bound to the mechanism-based inhibitor 5-fluoro-dUMP (FdUMP) and methylenetetrahydrofolate (CH2THF) have been determined to 2.6 and 2.2 A nominal resolutions, with crystallographic R factors of 0.180 and 0.178, respectively. The inhibitor and cofactor are well ordered in both structures and display covalent links to each other and to Cys 146 in the TS active site. The structures are in general agreement with a previous report for this complex (D. A. Matthews et al. (1990) J. Mol. Biol. 214, 937-948), but differ in two key respects: (i) the methylene bridge linking FdUMP and CH2THF is rotated about 60 degrees to a different position and (ii) the electron density for C6 of FdUMP, which is covalently linked to Cys 146, is more diffuse than for the other atoms in the pyrimidine ring. The ligand arrangement observed in the previous structure led the authors to propose that a large conformational change in ligand geometry must occur in order to facilitate catalysis and yield the correct chirality in the methyl of product dTMP. The new structures suggest a different mechanism for product formation that does not require ligands to greatly alter their conformations during catalysis and which makes use of instability in the nucleotide-Cys 146 thiol adduct to avoid a deep free energy well and assist in proton abstraction from dUMP. All intermediates in the proposed mechanism were modeled and energy minimized in the TS active site, and all can be accommodated in the present structures. The role of ligand-induced conformational change in the TS mechanism and the possibility of Tyr 94 acting as a base during catalysis are also discussed.
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===THYMIDYLATE SYNTHASE TERNARY COMPLEX WITH FDUMP AND METHYLENETETRAHYDROFOLATE===
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Use of strain in a stereospecific catalytic mechanism: crystal structures of Escherichia coli thymidylate synthase bound to FdUMP and methylenetetrahydrofolate.,Hyatt DC, Maley F, Montfort WR Biochemistry. 1997 Apr 15;36(15):4585-94. PMID:9109668<ref>PMID:9109668</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1tsn" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_9109668}}, adds the Publication Abstract to the page
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*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 9109668 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_9109668}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1TSN is a 1 chain 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=1TSN OCA].
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==Reference==
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<ref group="xtra">PMID:9109668</ref><references group="xtra"/>
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Thymidylate synthase]]
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[[Category: Large Structures]]
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[[Category: Hyatt, D C.]]
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[[Category: Hyatt DC]]
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[[Category: Maley, F.]]
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[[Category: Maley F]]
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[[Category: Montfort, W R.]]
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[[Category: Montfort WR]]
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[[Category: Methyltransferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 06:40:42 2009''
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Current revision

THYMIDYLATE SYNTHASE TERNARY COMPLEX WITH FDUMP AND METHYLENETETRAHYDROFOLATE

PDB ID 1tsn

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