2yoh: Difference between revisions

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-{{STRUCTURE_2yoh|  PDB=2yoh  |  SCENE=  }}
+==Plasmodium falciparum thymidylate kinase in complex with a urea-alpha- deoxythymidine inhibitor==
-===Plasmodium falciparum thymidylate kinase in complex with a urea-alpha- deoxythymidine inhibitor===
+<StructureSection load='2yoh' size='340' side='right' caption='[[2yoh]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
-{{ABSTRACT_PUBMED_23240776}}
+== 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).
-==About this Structure==
+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>
-[[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].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:023240776</ref><references group="xtra"/><references/>
+</div>
+==See Also==
+*[[Thymidylate kinase|Thymidylate kinase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Plasmodium falciparum 3d7]]
 [[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: Malaria]]
 [[Category: Transferase]]