2y8c
From Proteopedia
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| - | [[ | + | ==Plasmodium falciparum dUTPase in complex with a trityl ligand== |
| + | <StructureSection load='2y8c' size='340' side='right' caption='[[2y8c]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2y8c]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y8C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y8C FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DUQ:(2S)-2-[(2,4-DIOXOPYRIMIDIN-1-YL)METHYL]-N-(2-HYDROXYETHYL)-4-TRITYLOXY-BUTANAMIDE'>DUQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1vyq|1vyq]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </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=2y8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y8c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y8c RCSB], [http://www.ebi.ac.uk/pdbsum/2y8c PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report a series of beta-branched acyclic tritylated deoxyuridine analogues as inhibitors of Plasmodium falciparum deoxyuridine-5'-triphosphate nucleotidohydrolase (PfdUTPase), an enzyme involved in nucleotide metabolism that acts as first line of defence against uracil incorporation into DNA. Compounds were assayed against both PfdUTPase and intact parasites showing a correlation between enzyme inhibition and cellular assays. beta-Branched acyclic uridine analogues described here showed equal or slightly better potency and selectivity compared with previously reported analogues. The best inhibitor gave a K(i) of 0.5 muM against PfdUTPase with selectivity greater than 200-fold compared to the corresponding human enzyme and sub-micromolar growth inhibition of P. falciparum (EC(50) 0.6 muM). A crystal structure of the complex of PfdUTPase with one of the inhibitors shows that this acyclic derivative binds to the active site in a similar manner to that previously reported for a tritylated cyclic deoxyuridine derivative. | ||
| - | + | beta-Branched acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase.,Baragana B, McCarthy O, Sanchez P, Bosch-Navarrete C, Kaiser M, Brun R, Whittingham JL, Roberts SM, Zhou XX, Wilson KS, Johansson NG, Gonzalez-Pacanowska D, Gilbert IH Bioorg Med Chem. 2011 Apr 1;19(7):2378-91. Epub 2011 Feb 17. PMID:21411327<ref>PMID:21411327</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Deoxyuridine 5'-triphosphate nucleotidohydrolase|Deoxyuridine 5'-triphosphate nucleotidohydrolase]] | *[[Deoxyuridine 5'-triphosphate nucleotidohydrolase|Deoxyuridine 5'-triphosphate nucleotidohydrolase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: DUTP diphosphatase]] | [[Category: DUTP diphosphatase]] | ||
| - | [[Category: Baragana, B | + | [[Category: Baragana, B]] |
| - | [[Category: Bosch, C | + | [[Category: Bosch, C]] |
| - | [[Category: Brun, R | + | [[Category: Brun, R]] |
| - | [[Category: Gilbert, I H | + | [[Category: Gilbert, I H]] |
| - | [[Category: Gonzalez-Pacanowska, D | + | [[Category: Gonzalez-Pacanowska, D]] |
| - | [[Category: Johansson, N G | + | [[Category: Johansson, N G]] |
| - | [[Category: Kaiser, M | + | [[Category: Kaiser, M]] |
| - | [[Category: Mccarthy, O | + | [[Category: Mccarthy, O]] |
| - | [[Category: Roberts, S | + | [[Category: Roberts, S]] |
| - | [[Category: Sanchez, P | + | [[Category: Sanchez, P]] |
| - | [[Category: Whittingham, J L | + | [[Category: Whittingham, J L]] |
| - | [[Category: Wilson, K S | + | [[Category: Wilson, K S]] |
| - | [[Category: Zhou, X X | + | [[Category: Zhou, X X]] |
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Malaria]] | [[Category: Malaria]] | ||
Revision as of 22:48, 3 January 2015
Plasmodium falciparum dUTPase in complex with a trityl ligand
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