2yof: Difference between revisions
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<StructureSection load='2yof' size='340' side='right'caption='[[2yof]], [[Resolution|resolution]] 1.82Å' scene=''> | <StructureSection load='2yof' size='340' side='right'caption='[[2yof]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2yof]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2yof]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YOF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YOF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=74W: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'>74W</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=74W: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'>74W</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</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]], [[2yog|2yog]], [[2yoh|2yoh]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wwf|2wwf]], [[2wwg|2wwg]], [[2wwh|2wwh]], [[2wwi|2wwi]], [[2yog|2yog]], [[2yoh|2yoh]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2yof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yof OCA], [https://pdbe.org/2yof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yof RCSB], [https://www.ebi.ac.uk/pdbsum/2yof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yof ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
Revision as of 15:34, 27 April 2022
Plasmodium falciparum thymidylate kinase in complex with a (thio)urea- beta-deoxythymidine inhibitorPlasmodium falciparum thymidylate kinase in complex with a (thio)urea- beta-deoxythymidine inhibitor
Structural highlights
Publication Abstract from PubMedPlasmodium 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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