1f4e: Difference between revisions
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|PDB= 1f4e |SIZE=350|CAPTION= <scene name='initialview01'>1f4e</scene>, resolution 1.9Å | |PDB= 1f4e |SIZE=350|CAPTION= <scene name='initialview01'>1f4e</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPR:TOSYL-D-PROLINE'>TPR</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=[[1f4b|1F4B]], [[1f4c|1F4C]], [[1f4d|1F4D]], [[1f4f|1F4F]], [[1f4g|1F4G]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f4e OCA], [http://www.ebi.ac.uk/pdbsum/1f4e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f4e RCSB]</span> | |||
}} | }} | ||
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[[Category: Stroud, R M.]] | [[Category: Stroud, R M.]] | ||
[[Category: Wells, J A.]] | [[Category: Wells, J A.]] | ||
[[Category: crystal structure of e. coli thymidylate synthase complexed with tosyl-d-proline]] | [[Category: crystal structure of e. coli thymidylate synthase complexed with tosyl-d-proline]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:15:38 2008'' | ||
Revision as of 20:15, 30 March 2008
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| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Thymidylate synthase, with EC number 2.1.1.45 | ||||||
| Related: | 1F4B, 1F4C, 1F4D, 1F4F, 1F4G
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF E. COLI THYMIDYLATE SYNTHASE COMPLEXED WITH TOSYL-D-PROLINE
OverviewOverview
We report a strategy (called "tethering") to discover low molecular weight ligands ( approximately 250 Da) that bind weakly to targeted sites on proteins through an intermediary disulfide tether. A native or engineered cysteine in a protein is allowed to react reversibly with a small library of disulfide-containing molecules ( approximately 1,200 compounds) at concentrations typically used in drug screening (10 to 200 microM). The cysteine-captured ligands, which are readily identified by MS, are among the most stable complexes, even though in the absence of the covalent tether the ligands may bind very weakly. This method was applied to generate a potent inhibitor for thymidylate synthase, an essential enzyme in pyrimidine metabolism with therapeutic applications in cancer and infectious diseases. The affinity of the untethered ligand (K(i) approximately 1 mM) was improved 3,000-fold by synthesis of a small set of analogs with the aid of crystallographic structures of the tethered complex. Such site-directed ligand discovery allows one to nucleate drug design from a spatially targeted lead fragment.
About this StructureAbout this Structure
1F4E is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
Site-directed ligand discovery., Erlanson DA, Braisted AC, Raphael DR, Randal M, Stroud RM, Gordon EM, Wells JA, Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9367-72. PMID:10944209
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