1tsd

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1tsd.gif|left|200px]]<br /><applet load="1tsd" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:1tsd.gif|left|200px]]
-
caption="1tsd, resolution 1.95&Aring;" />
+
 
-
'''THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89'''<br />
+
{{Structure
 +
|PDB= 1tsd |SIZE=350|CAPTION= <scene name='initialview01'>1tsd</scene>, resolution 1.95&Aring;
 +
|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 [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=BME:'>BME</scene>, <scene name='pdbligand=UMP:'>UMP</scene> and <scene name='pdbligand=F89:'>F89</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1TSD OCA].
+
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=8846221 8846221]
+
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 Feb 21 15:16:54 2008''
+
''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

Image:1tsd.gif


PDB ID 1tsd

Drag the structure with the mouse to rotate
, resolution 1.95Å
Ligands: , and
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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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