1tsd: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1tsd.gif|left|200px]] | [[Image:1tsd.gif|left|200px]] | ||
'''THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89''' | {{Structure | ||
|PDB= 1tsd |SIZE=350|CAPTION= <scene name='initialview01'>1tsd</scene>, resolution 1.95Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=UMP:2'-DEOXYURIDINE+5'-MONOPHOSPHATE'>UMP</scene> and <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> | |||
|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] | |||
|GENE= | |||
}} | |||
'''THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1TSD is a [ | 1TSD 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=1TSD OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/8846221 8846221] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 22: | Line 31: | ||
[[Category: dump]] | [[Category: dump]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:22:31 2008'' | ||
Revision as of 12:22, 20 March 2008
| |||||||||||||
| 1tsd, resolution 1.95Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | BME, UMP and F89 | ||||||||||||
| Activity: | Thymidylate synthase, with EC number 2.1.1.45 | ||||||||||||
| 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
Page seeded by OCA on Thu Mar 20 14:22:31 2008
