2yog

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:06, 1 February 2024) (edit) (undo)
 
(4 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_2yog| PDB=2yog | SCENE= }}
 
-
===Plasmodium falciparum thymidylate kinase in complex with a (thio)urea- alpha-deoxythymidine inhibitor===
 
-
{{ABSTRACT_PUBMED_23240776}}
 
-
==About this Structure==
+
==Plasmodium falciparum thymidylate kinase in complex with a (thio)urea- alpha-deoxythymidine inhibitor==
-
[[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].
+
<StructureSection load='2yog' size='340' side='right'caption='[[2yog]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2yog]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2YOG FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2yog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yog OCA], [https://pdbe.org/2yog PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yog RCSB], [https://www.ebi.ac.uk/pdbsum/2yog PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yog ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/KTHY_PLAF7 KTHY_PLAF7] Catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), the immediate precursor for the DNA building block dTTP (PubMed:18477629, PubMed:19126267, PubMed:31934749, PubMed:20353400). Can also phosphorylate dGMP and to a lesser extent GMP, dUMP and dIMP (PubMed:18477629, PubMed:19126267, PubMed:31934749, PubMed:20353400). Can use either ATP or dATP as phosphate donors in presence of Mg(2+) (PubMed:18477629).<ref>PMID:18477629</ref> <ref>PMID:19126267</ref> <ref>PMID:20353400</ref> <ref>PMID:31934749</ref>
 +
<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).
-
==Reference==
+
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>
-
<ref group="xtra">PMID:023240776</ref><references group="xtra"/><references/>
+
 
-
[[Category: Plasmodium falciparum 3d7]]
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: DTMP kinase]]
+
</div>
-
[[Category: Brannigan, J A.]]
+
<div class="pdbe-citations 2yog" style="background-color:#fffaf0;"></div>
-
[[Category: Carrero-Lerida, J.]]
+
 
-
[[Category: Gilbert, I H.]]
+
==See Also==
-
[[Category: Gonzalez-Pacanowska, D.]]
+
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
-
[[Category: Huaqing, C.]]
+
== References ==
-
[[Category: Read, K D.]]
+
<references/>
-
[[Category: Ruiz-Perez, L M.]]
+
__TOC__
-
[[Category: Silva, A P.G.]]
+
</StructureSection>
-
[[Category: Whittingham, J L.]]
+
[[Category: Large Structures]]
-
[[Category: Wilson, K S.]]
+
[[Category: Plasmodium falciparum 3D7]]
-
[[Category: Inhibitor]]
+
[[Category: Brannigan JA]]
-
[[Category: Malaria]]
+
[[Category: Carrero-Lerida J]]
-
[[Category: Transferase]]
+
[[Category: Gilbert IH]]
 +
[[Category: Gonzalez-Pacanowska D]]
 +
[[Category: Huaqing C]]
 +
[[Category: Read KD]]
 +
[[Category: Ruiz-Perez LM]]
 +
[[Category: Silva APG]]
 +
[[Category: Whittingham JL]]
 +
[[Category: Wilson KS]]

Current revision

Plasmodium falciparum thymidylate kinase in complex with a (thio)urea- alpha-deoxythymidine inhibitor

PDB ID 2yog

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2yog"
Personal tools