This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2yoh
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==Plasmodium falciparum thymidylate kinase in complex with a urea-alpha- deoxythymidine inhibitor== | |
| - | ===Plasmodium falciparum thymidylate kinase in | + | <StructureSection load='2yoh' size='340' side='right' caption='[[2yoh]], [[Resolution|resolution]] 1.60Å' scene=''> |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[2yoh]] 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=2YOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YOH FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=WMJ:1-[[(2R,3S,5S)-5-[5-METHYL-2,4-BIS(OXIDANYLIDENE)PYRIMIDIN-1-YL]-3-OXIDANYL-OXOLAN-2-YL]METHYL]-3-(4-NITROPHENYL)UREA'>WMJ</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]]</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=2yoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yoh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yoh RCSB], [http://www.ebi.ac.uk/pdbsum/2yoh 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 13:45, 18 December 2014
Plasmodium falciparum thymidylate kinase in complex with a urea-alpha- deoxythymidine inhibitor
| |||||||||||
