Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lock, M. J.
Right arrow Articles by Emery, V. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lock, M. J.
Right arrow Articles by Emery, V. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of Antimicrobial Chemotherapy (2002) 49, 359-366
© 2002 The British Society for Antimicrobial Chemotherapy

Azidodeoxythymidine and didehydrodeoxythymidine as inhibitors and substrates of the human herpesvirus 8 thymidine kinase

Matthew J. Lock, Nicola Thorley, Jeanette Teo and Vincent C. Emery,*

Department of Virology, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, Hampstead, London NW3 2PF, UK

Human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi's sarcoma (KS), encodes many core genes that have been maintained during evolution of the Herpesviridae. Among these is a thymidine kinase (TK) homologue (ORF21), which has 12% homology to the related TK encoded by herpes simplex virus. We show that the HHV-8 TK is a functional deoxythymidine (dT) kinase, with Michaelis constants (Km) for dT and ATP of 18.5 and 6.6 µM, respectively. Using homology modelling coupled with site-directed mutagenesis, we identify Gly265, Asp362 and Phe372 as key amino acid residues involved in the catalytic process. The HHV-8 TK is competitively inhibited by azidodeoxythymidine (zidovudine) and didehydrodeoxythymidine (stavudine) and can also accept these anti-retroviral compounds as substrates. These data have implications for our understanding of changes in AIDS-KS incidence following the clinical licensing of these compounds and in the development of new therapies for KS.

* Corresponding author. Tel: +44-20-7830-2997; Fax: +44-20-7830-2854; E-mail: v.emery{at}rfc.ucl.ac.uk


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Virol.Home page
M. B. Gill, J. L. Kutok, and J. D. Fingeroth
Epstein-Barr Virus Thymidine Kinase Is a Centrosomal Resident Precisely Localized to the Periphery of Centrioles
J. Virol., June 15, 2007; 81(12): 6523 - 6535.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. B. Gill, J.-E. Murphy, and J. D. Fingeroth
Functional Divergence of Kaposi's Sarcoma-Associated Herpesvirus and Related Gamma-2 Herpesvirus Thymidine Kinases: Novel Cytoplasmic Phosphoproteins That Alter Cellular Morphology and Disrupt Adhesion
J. Virol., December 1, 2005; 79(23): 14647 - 14659.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
G. Gaspar, E. De Clercq, and J. Neyts
Human Herpesvirus 8 Gene Encodes a Functional Thymidylate Synthase
J. Virol., September 11, 2002; 76(20): 10530 - 10532.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.