2xx3: Difference between revisions
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==HUMAN THYMIDYLATE KINASE COMPLEXED WITH | |||
<StructureSection load='2xx3' size='340' side='right' caption='[[2xx3]], [[Resolution|resolution]] 2.00Å' scene=''> | ==HUMAN THYMIDYLATE KINASE COMPLEXED WITH thymidine butenyl phosphonate monophosphate and ADP== | ||
<StructureSection load='2xx3' size='340' side='right'caption='[[2xx3]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xx3]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2xx3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XX3 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=TAE:N1-[(E)-4-DIHYDROXYPHOSPHONYL-BUT-2-ENYL]-THYMINE'>TAE</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=TAE:N1-[(E)-4-DIHYDROXYPHOSPHONYL-BUT-2-ENYL]-THYMINE'>TAE</scene></td></tr> | |||
<tr | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xx3 OCA], [https://pdbe.org/2xx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xx3 RCSB], [https://www.ebi.ac.uk/pdbsum/2xx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xx3 ProSAT]</span></td></tr> | ||
</table> | |||
<table> | == Function == | ||
[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN] Catalyzes the conversion of dTMP to dTDP. | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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Novel antiviral C5-substituted pyrimidine acyclic nucleoside phosphonates selected as human thymidylate kinase substrates.,Topalis D, Pradere U, Roy V, Caillat C, Azzouzi A, Broggi J, Snoeck R, Andrei G, Lin J, Eriksson S, Alexandre JA, El-Amri C, Deville-Bonne D, Meyer P, Balzarini J, Agrofoglio LA J Med Chem. 2011 Jan 13;54(1):222-32. Epub 2010 Dec 3. PMID:21128666<ref>PMID:21128666</ref> | Novel antiviral C5-substituted pyrimidine acyclic nucleoside phosphonates selected as human thymidylate kinase substrates.,Topalis D, Pradere U, Roy V, Caillat C, Azzouzi A, Broggi J, Snoeck R, Andrei G, Lin J, Eriksson S, Alexandre JA, El-Amri C, Deville-Bonne D, Meyer P, Balzarini J, Agrofoglio LA J Med Chem. 2011 Jan 13;54(1):222-32. Epub 2010 Dec 3. PMID:21128666<ref>PMID:21128666</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2xx3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Caillat | [[Category: Caillat C]] | ||
[[Category: Meyer | [[Category: Meyer P]] | ||
Latest revision as of 17:00, 1 February 2024
HUMAN THYMIDYLATE KINASE COMPLEXED WITH thymidine butenyl phosphonate monophosphate and ADPHUMAN THYMIDYLATE KINASE COMPLEXED WITH thymidine butenyl phosphonate monophosphate and ADP
Structural highlights
FunctionKTHY_HUMAN Catalyzes the conversion of dTMP to dTDP. Publication Abstract from PubMedAcyclic nucleoside phosphonates (ANPs) are at the cornerstone of DNA virus and retrovirus therapies. They reach their target, the viral DNA polymerase, after two phosphorylation steps catalyzed by cellular kinases. New pyrimidine ANPs have been synthesized with unsaturated acyclic side chains (prop-2-enyl-, but-2-enyl-, pent-2-enyl-) and different substituents at the C5 position of the uracil nucleobase. Several derivatives in the but-2-enyl- series 9d and 9e, with (E) but not with (Z) configuration, were efficient substrates for human thymidine monophosphate (TMP) kinase, but not for uridine monophosphate-cytosine monophosphate (UMP-CMP) kinase, which is in contrast to cidofovir. Human TMP kinase was successfully crystallized in a complex with phosphorylated (E)-thymidine-but-2-enyl phosphonate 9e and ADP. The bis-pivaloyloxymethyl (POM) esters of (E)-9d and (E)-9e were synthesized and shown to exert activity against herpes virus in vitro (IC(50) = 3 muM) and against varicella zoster virus in vitro (IC(50) = 0.19 muM), in contrast to the corresponding inactive (Z) derivatives. Thus, their antiviral activity correlates with their ability to act as thymidylate kinase substrates. Novel antiviral C5-substituted pyrimidine acyclic nucleoside phosphonates selected as human thymidylate kinase substrates.,Topalis D, Pradere U, Roy V, Caillat C, Azzouzi A, Broggi J, Snoeck R, Andrei G, Lin J, Eriksson S, Alexandre JA, El-Amri C, Deville-Bonne D, Meyer P, Balzarini J, Agrofoglio LA J Med Chem. 2011 Jan 13;54(1):222-32. Epub 2010 Dec 3. PMID:21128666[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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