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1tsd

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Revision as of 16:15, 27 October 2021

THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89

Structural highlights

1tsd is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:
Activity:	Thymidylate synthase, with EC number 2.1.1.45
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The anticancer drug 1843U89 inhibits thymidylate synthase (TS) at sub-nanomolar concentrations and is undergoing clinical trial. The 1.95 A crystal structure of Escherichia coli TS bound to the drug and dUMP reveals that the 1843U89 binding surface includes a hydrophobic patch that is normally buried. To reach this patch, 1843U89 inserts into the wall of the TS active site, resulting in a severe local distortion of the protein. In this new conformation, active-site groups that normally bind to the catalytic cofactor methylene-tetrahydrofolate instead bind to 1843U89 in new ways. This structure provides a rare example of a protein that can bind tightly to distinct substances using a single, flexible, binding surface. This has implications for drug design, as 1843U89 could not have been obtained from current structure-based approaches.

Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89.,Weichsel A, Montfort WR Nat Struct Biol. 1995 Dec;2(12):1095-101. PMID:8846221^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Weichsel A, Montfort WR. Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89. Nat Struct Biol. 1995 Dec;2(12):1095-101. PMID:8846221

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1tsd"

@@ Line 3: / Line 3: @@
 <StructureSection load='1tsd' size='340' side='right'caption='[[1tsd]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1tsd]] 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=1TSD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TSD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1tsd]] is a 2 chain structure with sequence from [https://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=1TSD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TSD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=F89:S)-2-(5(((1,2-DIHYDRO-3-METHYL-1-OXOBENZO(F)QUINAZOLIN-9-YL)METHYL)AMINO)1-OXO-2-ISOINDOLINYL)GLUTARIC+ACID'>F89</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
+</td></tr><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=F89:S)-2-(5(((1,2-DIHYDRO-3-METHYL-1-OXOBENZO(F)QUINAZOLIN-9-YL)METHYL)AMINO)1-OXO-2-ISOINDOLINYL)GLUTARIC+ACID'>F89</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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='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'>[https://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [https://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=1tsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tsd OCA], [http://pdbe.org/1tsd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tsd RCSB], [http://www.ebi.ac.uk/pdbsum/1tsd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tsd 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=1tsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tsd OCA], [https://pdbe.org/1tsd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tsd RCSB], [https://www.ebi.ac.uk/pdbsum/1tsd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tsd ProSAT]</span></td></tr>
 </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.
+[[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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 32: @@
 ==See Also==
-*[[Thymidylate synthase|Thymidylate synthase]]
+*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
 == References ==
 <references/>

1tsd

From Proteopedia

Revision as of 16:15, 27 October 2021

THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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