1tsd
From Proteopedia
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|PDB= 1tsd |SIZE=350|CAPTION= <scene name='initialview01'>1tsd</scene>, resolution 1.95Å | |PDB= 1tsd |SIZE=350|CAPTION= <scene name='initialview01'>1tsd</scene>, resolution 1.95Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, | + | |LIGAND= <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=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=UMP:2'-DEOXYURIDINE+5'-MONOPHOSPHATE'>UMP</scene> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<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://www.ebi.ac.uk/pdbsum/1tsd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tsd RCSB]</span> | ||
}} | }} | ||
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[[Category: Montfort, W R.]] | [[Category: Montfort, W R.]] | ||
[[Category: Weichsel, A.]] | [[Category: Weichsel, A.]] | ||
| - | [[Category: BME]] | ||
| - | [[Category: F89]] | ||
| - | [[Category: UMP]] | ||
[[Category: 1843u89]] | [[Category: 1843u89]] | ||
[[Category: dump]] | [[Category: dump]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:00:24 2008'' |
Revision as of 21:00, 30 March 2008
| |||||||
| , resolution 1.95Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Thymidylate synthase, with EC number 2.1.1.45 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89
Overview
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.
About this Structure
1TSD is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
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
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