Structural highlights
Function
[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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martic M, Pernot L, Westermaier Y, Perozzo R, Kraljevic TG, Kristafor S, Raic-Malic S, Scapozza L, Ametamey S. Synthesis, crystal structure, and in vitro biological evaluation of C-6 pyrimidine derivatives: new lead structures for monitoring gene expression in vivo. Nucleosides Nucleotides Nucleic Acids. 2011 Apr;30(4):293-315. PMID:21623543 doi:10.1080/15257770.2011.581258
