View source for 4isk

==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]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4isk]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ISK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ISK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1JY:N-(4-{[(6S)-2-(HYDROXYMETHYL)-4-OXO-4,6,7,8-TETRAHYDRO-1H-CYCLOPENTA[G]QUINAZOLIN-6-YL](PROP-2-YN-1-YL)AMINO}BENZOYL)-L-GAMMA-GLUTAMYL-D-GLUTAMIC+ACID'>1JY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=UMC:2-DEOXY-5-URIDYLIC+ACID'>UMC</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kce|2kce]], [[1hvy|1hvy]], [[1an5|1an5]], [[1axw|1axw]]</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='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>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 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<ref>PMID:23710599</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Thymidylate synthase|Thymidylate synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ecoli]]
[[Category: Thymidylate synthase]]
[[Category: Finer-Moore, J]]
[[Category: Stroud, R M]]
[[Category: Tochowicz, A]]
[[Category: Alpha/beta protein]]
[[Category: Dump subtrate]]
[[Category: Methylase]]
[[Category: Methyltransferase]]
[[Category: Transferase-transferase inhibitor complex]]