2yog
From Proteopedia
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| - | + | ==Plasmodium falciparum thymidylate kinase in complex with a (thio)urea- alpha-deoxythymidine inhibitor== | |
| - | + | <StructureSection load='2yog' size='340' side='right' caption='[[2yog]], [[Resolution|resolution]] 1.50Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[2yog]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum_3d7 Plasmodium falciparum 3d7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YOG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YOG FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=74X:1-[4-CHLORANYL-3-(TRIFLUOROMETHYL)PHENYL]-3-[[(2R,3S)-5-[5-METHYL-2,4-BIS(OXIDANYLIDENE)PYRIMIDIN-1-YL]-3-OXIDANYL-OXOLAN-2-YL]METHYL]THIOUREA'>74X</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wwf|2wwf]], [[2wwg|2wwg]], [[2wwh|2wwh]], [[2wwi|2wwi]], [[2yof|2yof]], [[2yoh|2yoh]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </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=2yog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yog OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yog RCSB], [http://www.ebi.ac.uk/pdbsum/2yog PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Plasmodium falciparum thymidylate kinase (PfTMPK) is a key enzyme in pyrimidine nucleotide biosynthesis. 3-Trifluoromethyl-4-chloro-phenyl-urea-alpha-thymidine has been reported as an inhibitor of Mycobacterium tuberculosis TMPK (MtTMPK). Starting from this point, we designed, synthesized and evaluated a number of thymidine analogues as antimalarials. Both 5'-urea-alpha- and beta-thymidine derivatives were moderate inhibitors of PfTMPK and furthermore showed moderate inhibition of parasite growth. The structure of several enzyme-inhibitor complexes provides a basis for improved inhibitor design. However, we found that certain 5'-urea-alpha-thymidine analogues had antimalarial activity where inhibition of PfTMPK is not the major mode of action. Optimization of this series resulted in a compound with potent antimalarial activity (EC(50) = 28 nM; CC(50) = 29 muM). | ||
| - | + | Synthesis and evaluation of alpha-thymidine analogues as novel antimalarials.,Cui H, Carrero-Lerida J, Silva AP, Whittingham JL, Brannigan JA, Ruiz-Perez LM, Read KD, Wilson KS, Gonzalez-Pacanowska D, Gilbert IH J Med Chem. 2012 Dec 27;55(24):10948-57. doi: 10.1021/jm301328h. Epub 2012 Dec, 14. PMID:23240776<ref>PMID:23240776</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | |||
| + | ==See Also== | ||
| + | *[[Thymidylate kinase|Thymidylate kinase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Plasmodium falciparum 3d7]] | [[Category: Plasmodium falciparum 3d7]] | ||
[[Category: DTMP kinase]] | [[Category: DTMP kinase]] | ||
| - | [[Category: Brannigan, J A | + | [[Category: Brannigan, J A]] |
| - | [[Category: Carrero-Lerida, J | + | [[Category: Carrero-Lerida, J]] |
| - | [[Category: Gilbert, I H | + | [[Category: Gilbert, I H]] |
| - | [[Category: Gonzalez-Pacanowska, D | + | [[Category: Gonzalez-Pacanowska, D]] |
| - | [[Category: Huaqing, C | + | [[Category: Huaqing, C]] |
| - | [[Category: Read, K D | + | [[Category: Read, K D]] |
| - | [[Category: Ruiz-Perez, L M | + | [[Category: Ruiz-Perez, L M]] |
| - | [[Category: Silva, A P.G | + | [[Category: Silva, A P.G]] |
| - | [[Category: Whittingham, J L | + | [[Category: Whittingham, J L]] |
| - | [[Category: Wilson, K S | + | [[Category: Wilson, K S]] |
[[Category: Inhibitor]] | [[Category: Inhibitor]] | ||
[[Category: Malaria]] | [[Category: Malaria]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 13:36, 18 December 2014
Plasmodium falciparum thymidylate kinase in complex with a (thio)urea- alpha-deoxythymidine inhibitor
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