1w4r

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Image:1w4r.gif

1w4r, resolution 1.83Å

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STRUCTURE OF A TYPE II THYMIDINE KINASE WITH BOUND DTTP

Overview

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.

About this Structure

1W4R is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Thymidine kinase, with EC number 2.7.1.21 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure of a type II thymidine kinase with bound dTTP., Birringer MS, Claus MT, Folkers G, Kloer DP, Schulz GE, Scapozza L, FEBS Lett. 2005 Feb 28;579(6):1376-82. PMID:15733844

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