4isk: Difference between revisions
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==Crystal structure of E.coli thymidylate synthase with dUMP and the BGC 945 inhibitor== | ==Crystal structure of E.coli thymidylate synthase with dUMP and the BGC 945 inhibitor== | ||
<StructureSection load='4isk' size='340' side='right' caption='[[4isk]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='4isk' size='340' side='right' caption='[[4isk]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thyA, b2827, JW2795 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thyA, b2827, JW2795 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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'>[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='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=4isk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4isk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4isk RCSB], [http://www.ebi.ac.uk/pdbsum/4isk PDBsum]</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=4isk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4isk OCA], [http://pdbe.org/4isk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4isk RCSB], [http://www.ebi.ac.uk/pdbsum/4isk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4isk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4isk" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 14:37, 5 August 2016
Crystal structure of E.coli thymidylate synthase with dUMP and the BGC 945 inhibitorCrystal structure of E.coli thymidylate synthase with dUMP and the BGC 945 inhibitor
Structural highlights
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. Publication Abstract from PubMedN-[4-[2-Propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta [g]quinazolin-6-yl]amino]benzoyl]-l-gamma-glutamyl-d-glutamic acid 1 (BGC 945, now known as ONX 0801), is a small molecule thymidylate synthase (TS) inhibitor discovered at the Institute of Cancer Research in London. It is licensed by Onyx Pharmaceuticals and is in phase 1 clinical studies. It is a novel antifolate drug resembling TS inhibitors plevitrexed and raltitrexed that combines enzymatic inhibition of thymidylate synthase with alpha-folate receptor-mediated targeting of tumor cells. Thus, it has potential for efficacy with lower toxicity due to selective intracellular accumulation through alpha-folate receptor (alpha-FR) transport. The alpha-FR, a cell-surface receptor glycoprotein, which is overexpressed mainly in ovarian and lung cancer tumors, has an affinity for 1 similar to that for its natural ligand, folic acid. This study describes a novel synthesis of 1, an X-ray crystal structure of its complex with Escherichia coli TS and 2'-deoxyuridine-5'-monophosphate, and a model for a similar complex with human TS. Development and Binding Mode Assessment of N-[4-[2-Propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta [g]quinazolin-6-yl]amino]benzoyl]-l-gamma-glutamyl-d-glutamic Acid (BGC 945), a Novel Thymidylate Synthase Inhibitor That Targets Tumor Cells.,Tochowicz A, Dalziel S, Eidam O, O'Connell JD 3rd, Griner S, Finer-Moore JS, Stroud RM J Med Chem. 2013 Jun 21. PMID:23710599[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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