Substrate specificity and molecular modelling of the feline herpesvirus-1 thymidine kinase

Archives of Virology
Islam T M HusseinHugh J Field

Abstract

Feline herpesvirus-1 (FHV-1) causes a severe upper respiratory and ocular disease in cats. An effective antiviral compound is required for treating FHV-1 infections. The virus-encoded thymidine kinase (TK) is the molecular basis for selective activation of commonly used antiviral nucleoside analogue drugs, e.g. acyclovir (ACV), penciclovir (PCV) and ganciclovir (GCV). The substrate specificity of a recombinant FHV-1 TK, expressed in Escherichia coli, was studied. FHV-1 TK efficiently phosphorylated its natural substrate deoxythymidine. However, it exhibited relatively lower affinity for the guanosine analogue substrates. PCV was most efficiently phosphorylated, followed by GCV, with approximately twofold reduction in the phosphorylation rate. The lowest phosphorylation rate was recorded for ACV. To correlate these biochemical data with structural features of the FHV-1 TK, a three-dimensional (3D) model of this enzyme was constructed based on sequence homology with two other herpesviral TKs, encoded by equine herpesvirus-4 (EHV-4) and herpes simplex-1 (HSV-1). Mutational analysis of the amino acids forming the FHV-1 TK active site identified two residues (Y29 and F144) as being critical for the differential ability of this enzym...Continue Reading

References

Jan 1, 1992·Pharmacology & Therapeutics·G A Gentry
Mar 5, 1992·Nature·R LüthyD Eisenberg
Oct 1, 1991·The Journal of General Virology·P T HarrisonA J Davison
Sep 1, 1983·The Journal of Antimicrobial Chemotherapy·P Collins
Dec 1, 1982·Biochemical Pharmacology·W H Miller, R L Miller
Oct 1, 1994·Protein Expression and Purification·J FetzerG Folkers
Jan 1, 1994·Mammalian Genome : Official Journal of the International Mammalian Genome Society·B M WinkesG S Barsh
May 20, 1994·Journal of Molecular Biology·I K McDonald, J M Thornton
Jan 1, 1993·Journal of Medical Virology·G B Elion
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Dec 14, 1993·Biochemical Pharmacology·G B RobertsT A Krenitsky
Aug 5, 1996·Biochemical and Biophysical Research Communications·S Gerber, G Folkers
Dec 1, 1996·Journal of Veterinary Pharmacology and Therapeutics·J G OwensD C Dorman
Aug 1, 1997·Computer Applications in the Biosciences : CABIOS·R W HooftG Vriend
Oct 23, 1997·Protein Science : a Publication of the Protein Society·K WildG E Schulz
Sep 25, 1998·The Journal of General Virology·J S EvansA Buchan
Oct 9, 1999·Veterinary Microbiology·R Gaskell, K Willoughby
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·M A Martí-RenomA Sali
Jun 16, 2001·Antimicrobial Agents and Chemotherapy·J M LoutschR Tal-Singer
Oct 6, 2001·Science·D Baker, A Sali
Nov 22, 2001·Journal of Feline Medicine and Surgery·S E Andrew
Jan 30, 2002·The Journal of Antimicrobial Chemotherapy·Matthew J LockVincent C Emery
Jul 18, 2002·Nature Reviews. Drug Discovery·Tom L BlundellChris Abell
Nov 8, 2003·Clinical Techniques in Small Animal Practice·Jean Stiles
Apr 14, 2004·American Journal of Veterinary Research·David J Maggs, Heather E Clarke
Apr 28, 2004·The Veterinary Clinics of North America. Small Animal Practice·Laurence E Galle
Jul 29, 2004·Drug Discovery Today·Alexander HillischRolf Hilgenfeld
Jun 14, 2005·Clinical Techniques in Small Animal Practice·David J Maggs
Jun 22, 2005·Expert Review of Proteomics·András Fiser
Mar 3, 2006·Current Opinion in Structural Biology·Krzysztof Ginalski
Sep 8, 2006·Antiviral Chemistry & Chemotherapy·Erik De ClercqHugh J Field

❮ Previous
Next ❯

Citations

Apr 4, 2009·Wiener medizinische Wochenschrift·Marco Wiltgen, Gernot P Tilz
Oct 12, 2010·The Veterinary Clinics of North America. Small Animal Practice·David J Maggs
May 6, 2008·Antiviral Research·N SolaroliA Karlsson
Apr 20, 2016·Veterinary Ophthalmology·Sara M Thomasy, David J Maggs

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.