1hvy

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(New page: 200px<br /> <applet load="1hvy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hvy, resolution 1.90&Aring;" /> '''Human thymidylate s...)
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[[Image:1hvy.gif|left|200px]]<br />
 
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<applet load="1hvy" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1hvy, resolution 1.90&Aring;" />
 
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'''Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation'''<br />
 
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==Overview==
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==Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation==
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Thymidylate synthase (TS) is a major target in the chemotherapy of, colorectal cancer and some other neoplasms while raltitrexed (Tomudex, ZD1694) is an antifolate inhibitor of TS approved for clinical use in, several European countries. The crystal structure of the complex between, recombinant human TS, dUMP, and raltitrexed has been determined at 1.9 A, resolution. In contrast to the situation observed in the analogous complex, of the rat TS, the enzyme is in the closed conformation and a covalent, bond between the catalytic Cys 195 and dUMP is present in both subunits., This mode of ligand binding is similar to that of the analogous complex of, the Escherichia coli enzyme. The only major differences observed are a, direct hydrogen bond between His 196 and the O4 atom of dUMP and, repositioning of the side chain of Tyr 94 by about 2 A. The thiophene ring, of the drug is disordered between two parallel positions.
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<StructureSection load='1hvy' size='340' side='right'caption='[[1hvy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1hvy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HVY FirstGlance]. <br>
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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]] 1.9&#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=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=D16:TOMUDEX'>D16</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
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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=1hvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hvy OCA], [https://pdbe.org/1hvy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hvy RCSB], [https://www.ebi.ac.uk/pdbsum/1hvy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hvy ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>
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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/hv/1hvy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1hvy ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Timothy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114205 114205]]
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*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1HVY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with D16, UMP and BME as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HVY OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug., Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L, Biochemistry. 2001 Feb 20;40(7):1897-902. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11329255 11329255]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Thymidylate synthase]]
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[[Category: Berger SH]]
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[[Category: Berger, S.H.]]
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[[Category: Dunlap RB]]
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[[Category: Dunlap, R.B.]]
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[[Category: Koli S]]
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[[Category: Koli, S.]]
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[[Category: Lebioda L]]
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[[Category: Lebioda, L.]]
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[[Category: Minor W]]
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[[Category: Minor, W.]]
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[[Category: Phan J]]
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[[Category: Phan, J.]]
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[[Category: BME]]
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[[Category: D16]]
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[[Category: UMP]]
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[[Category: raltitrexed]]
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[[Category: tomudex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:23:20 2007''
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Current revision

Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation

PDB ID 1hvy

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