3rdp: Difference between revisions
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==Crystal structure of thymidine kinase from herpes simplex virus type 1 in complex with N-METHYL-FHBT== | |||
<StructureSection load='3rdp' size='340' side='right'caption='[[3rdp]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3rdp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1_strain_17 Human alphaherpesvirus 1 strain 17]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RDP 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NMF:6-[(2R)-2-(FLUOROMETHYL)-3-HYDROXY-PROPYL]-1,5-DIMETHYL-PYRIMIDINE-2,4-DIONE'>NMF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3rdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rdp OCA], [https://pdbe.org/3rdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rdp RCSB], [https://www.ebi.ac.uk/pdbsum/3rdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rdp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KITH_HHV11 KITH_HHV11] In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to "gold standard" 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (K(m) = 10 +/- 0.3 muM; k(cat) = 0.036 +/- 0.015 sec(-1)). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues. | |||
Synthesis, crystal structure, and in vitro biological evaluation of C-6 pyrimidine derivatives: new lead structures for monitoring gene expression in vivo.,Martic M, Pernot L, Westermaier Y, Perozzo R, Kraljevic TG, Kristafor S, Raic-Malic S, Scapozza L, Ametamey S Nucleosides Nucleotides Nucleic Acids. 2011 Apr;30(4):293-315. PMID:21623543<ref>PMID:21623543</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3rdp" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thymidine kinase 3D structures|Thymidine kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human alphaherpesvirus 1 strain 17]] | |||
[[Category: Large Structures]] | |||
[[Category: Ametamey S]] | |||
[[Category: Martic M]] | |||
[[Category: Pernot L]] | |||
[[Category: Perozzo R]] | |||
[[Category: Scapozza L]] | |||
[[Category: Westermaier Y]] | |||
Latest revision as of 17:16, 1 November 2023
Crystal structure of thymidine kinase from herpes simplex virus type 1 in complex with N-METHYL-FHBT
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