Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.
Article Details
- CitationCopy to clipboard
Suzuki NN, Koizumi K, Fukushima M, Matsuda A, Inagaki F
Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.
Structure. 2004 May;12(5):751-64.
- PubMed ID
- 15130468 [ View in PubMed]
- Abstract
Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine and cytidine and activates pharmacological ribonucleoside analogs. Here we present the crystal structures of human UCK alone and in complexes with a substrate, cytidine, a feedback inhibitor, CTP or UTP, and with phosphorylation products, CMP and ADP, respectively. Free UCK takes an alpha/beta mononucleotide binding fold and exists as a homotetramer with 222 symmetry. Upon inhibitor binding, one loop region was loosened, causing the UCK tetramer to be distorted. Upon cytidine binding, a large induced fit was observed at the uridine/cytidine binding site, which endows UCK with a strict specificity for pyrimidine ribonucleosides. The first UCK structure provided the structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase, which give clues for the design of novel antitumor and antiviral ribonucleoside analogs that inhibit RNA synthesis.