2orv
human Thymidine Kinase 1 in complex with TP4A
|
OverviewOverview
Human thymidine kinase 1 (hTK1) and structurally related TKs from other, organisms catalyze the initial phosphorylation step in the thymidine, salvage pathway. Though ATP is known to be the preferred phosphoryl donor, for TK1-like enzymes, its exact binding mode and effect on the oligomeric, state has not been analyzed. Here we report the structures of hTK1 and of, the Thermotoga maritima thymidine kinase (TmTK) in complex with the, bisubstrate inhibitor TP4A. The TmTK-TP4A structure reveals that the, adenosine moiety of ATP binds at the subunit interface of the, homotetrameric enzyme and that the majority of the ATP-enzyme interactions, occur between the phosphate groups and the P-loop. In the hTK1 structure, the adenosine group of TP4A exhibited no electron density. This difference, between hTK1 and TmTK is rationalized by a difference in the conformation, of their quaternary structure. A more open conformation, as seen in the, TmTK-TP4A complex structure, is required to provide space for the, adenosine moiety. Our analysis supports the formation of an analogous open, conformation in hTK1 upon ATP binding.
About this StructureAbout this Structure
2ORV is a Single protein structure of sequence from Homo sapiens with ZN and 4TA as ligands. Active as Thymidine kinase, with EC number 2.7.1.21 Full crystallographic information is available from OCA.
ReferenceReference
Binding of ATP to TK1-like Enzymes Is Associated with a Conformational Change in the Quaternary Structure., Segura-Pena D, Lutz S, Monnerjahn C, Konrad M, Lavie A, J Mol Biol. 2007 May 25;369(1):129-41. Epub 2007 Mar 15. PMID:17407781
Page seeded by OCA on Mon Nov 12 23:15:26 2007