2QQE

Thymidine Kinase from Thermotoga Maritima in complex with Thymidine

Summary for 2QQE

• Entry DOI: 10.2210/pdb2qqe/pdb
• Related: 2QPO 2QQ0
• Descriptor: Thymidine kinase, ZINC ION, THYMIDINE, ... (4 entities in total)
• Functional Keywords: tmtk in complex with thymidine, close conformation, atp-binding, cytoplasm, dna synthesis, kinase, nucleotide-binding, transferase
• Biological source: Thermotoga maritima
• Cellular location: Cytoplasm (Potential): Q9WYN2
• Total number of polymer chains: 2
• Total formula weight: 41985.12

Authors

Segura-Pena, D.,Lichter, J.,Trani, M.,Konrad, M.,Lavie, A.,Lutz, S. (deposition date: 2007-07-26, release date: 2007-10-16, Last modification date: 2024-02-21)

Primary citation

Segura-Pena, D.,Lichter, J.,Trani, M.,Konrad, M.,Lavie, A.,Lutz, S.
Quaternary structure change as a mechanism for the regulation of thymidine kinase 1-like enzymes.
Structure, 15:1555-1566, 2007

PubMed Abstract: The human cytosolic thymidine kinase (TK) and structurally related TKs in prokaryotes play a crucial role in the synthesis and regulation of the cellular thymidine triphosphate pool. We report the crystal structures of the TK homotetramer from Thermotoga maritima in four different states: its apo-form, a binary complex with thymidine, as well as the ternary structures with the two substrates (thymidine/AppNHp) and the reaction products (TMP/ADP). In combination with fluorescence spectroscopy and mutagenesis experiments, our results demonstrate that ATP binding is linked to a substantial reorganization of the enzyme quaternary structure, leading to a transition from a closed, inactive conformation to an open, catalytic state. We hypothesize that these structural changes are relevant to enzyme function in situ as part of the catalytic cycle and serve an important role in regulating enzyme activity by amplifying the effects of feedback inhibitor binding.

PubMed: 18073106
DOI: 10.1016/j.str.2007.09.025

Experimental method

X-RAY DIFFRACTION (1.9 Å)