1W4R

Structure of a type II thymidine kinase with bound dTTP

Summary for 1W4R

• Entry DOI: 10.2210/pdb1w4r/pdb
• Descriptor: THYMIDINE KINASE, THYMIDINE-5'-TRIPHOSPHATE, ZINC ION, ... (5 entities in total)
• Functional Keywords: transferase, type ii
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P04183
• Total number of polymer chains: 8
• Total formula weight: 178842.27

Authors

Birringer, M.S.,Claus, M.T.,Folkers, G.,Kloer, D.P.,Schulz, G.E.,Scapozza, L. (deposition date: 2004-07-27, release date: 2005-02-01, Last modification date: 2013-03-06)

Primary citation

Birringer, M.S.,Claus, M.T.,Folkers, G.,Kloer, D.P.,Schulz, G.E.,Scapozza, L.
Structure of a Type II Thymidine Kinase with Bound Dttp
FEBS Lett., 579:1376-, 2005

PubMed 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.

PubMed: 15733844
DOI: 10.1016/J.FEBSLET.2005.01.034

Experimental method

X-RAY DIFFRACTION (1.83 Å)