3f0t

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3f0t, resolution 2.00Å ()
Ligands: ,
Gene: TK, UL23 (Herpes simplex virus (type 1 / strain 17))
Activity: Thymidine kinase, with EC number 2.7.1.21
Related: 1e2p, 1e2h
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal structure of thymidine kinase from Herpes simplex virus type 1 in complex with N-methyl-DHBT

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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).

About this Structure

3f0t is a 2 chain structure with sequence from Herpes simplex virus (type 1 / strain 17). Full crystallographic information is available from OCA.

See Also

Reference

  • 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

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