Structure of a type II thymidine kinase with bound dTTP.
FEBS Lett
; 579(6): 1376-82, 2005 Feb 28.
Article
em En
| MEDLINE
| ID: mdl-15733844
ABSTRACT
The structure of human cytosolic thymidine kinase in complex with its feedback inhibitor 2'-deoxythymidine-5'-triphosphate was determined. This structure is the first representative of the type II thymidine kinases found in several pathogens. The structure deviates strongly from the known structures of type I thymidine kinases such as the Herpes simplex enzyme. It contains a zinc-binding domain with four cysteines complexing a structural zinc ion. Interestingly, the backbone atoms of the type II enzyme bind thymine via hydrogen-bonds, in contrast to type I, where side chains are involved. This results in a specificity difference exploited for antiviral therapy. The presented structure will foster the development of new drugs and prodrugs for numerous therapeutic applications.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timidina Quinase
/
Nucleotídeos de Timina
Limite:
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article