2xx3: Difference between revisions

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[[Image:2xx3.jpg|left|200px]]
==HUMAN THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE BUTENYL PHOSPHONATE MONOPHOSPHATE AND ADP==
<StructureSection load='2xx3' size='340' side='right' caption='[[2xx3]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xx3]] is a 1 chain structure with sequence from [http://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]. <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><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1e2d|1e2d]], [[1e2g|1e2g]], [[1e9a|1e9a]], [[1e9b|1e9b]], [[1e98|1e98]], [[1nn3|1nn3]], [[1e2e|1e2e]], [[1e9e|1e9e]], [[1e2q|1e2q]], [[1e99|1e99]], [[1nmx|1nmx]], [[1nn5|1nn5]], [[1nmz|1nmz]], [[1nn1|1nn1]], [[1e9d|1e9d]], [[1nmy|1nmy]], [[1e2f|1e2f]], [[1nn0|1nn0]], [[1e9f|1e9f]], [[1e9c|1e9c]]</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xx3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xx3 RCSB], [http://www.ebi.ac.uk/pdbsum/2xx3 PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Acyclic 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.


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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>
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{{STRUCTURE_2xx3|  PDB=2xx3  |  SCENE=  }}


===HUMAN THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE BUTENYL PHOSPHONATE MONOPHOSPHATE AND ADP===
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
 
</div>
 
== References ==
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{{ABSTRACT_PUBMED_21128666}}
 
==About this Structure==
[[2xx3]] is a 1 chain structure with sequence from [http://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].
 
==Reference==
<ref group="xtra">PMID:021128666</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: DTMP kinase]]
[[Category: DTMP kinase]]

Revision as of 10:51, 14 May 2014

HUMAN THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE BUTENYL PHOSPHONATE MONOPHOSPHATE AND ADPHUMAN THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE BUTENYL PHOSPHONATE MONOPHOSPHATE AND ADP

Structural highlights

2xx3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Ligands:, , ,
Related:1e2d, 1e2g, 1e9a, 1e9b, 1e98, 1nn3, 1e2e, 1e9e, 1e2q, 1e99, 1nmx, 1nn5, 1nmz, 1nn1, 1e9d, 1nmy, 1e2f, 1nn0, 1e9f, 1e9c
Activity:Glucokinase, with EC number 2.7.1.2
Resources:FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

Acyclic 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.

References

  1. ↑ 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. Novel antiviral C5-substituted pyrimidine acyclic nucleoside phosphonates selected as human thymidylate kinase substrates. J Med Chem. 2011 Jan 13;54(1):222-32. Epub 2010 Dec 3. PMID:21128666 doi:10.1021/jm1011462

2xx3, resolution 2.00Å

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