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Structure. 2004 May;12(5):751-64.

Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.

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1
Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12 W6 Kita-ku, Sapporo 060-0812, Japan.

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.

PMID:
15130468
DOI:
10.1016/j.str.2004.02.038
[Indexed for MEDLINE]
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