1UDW

Crystal structure of human uridine-cytidine kinase 2 complexed with a feedback-inhibitor, CTP

Summary for 1UDW

• Entry DOI: 10.2210/pdb1udw/pdb
• Descriptor: Uridine-cytidine kinase 2, CYTIDINE-5'-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: alpha/beta mononucleotide-binding hold, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 57492.30

Authors

Suzuki, N.N.,Koizumi, K.,Fukushima, M.,Matsuda, A.,Inagaki, F. (deposition date: 2003-05-07, release date: 2004-05-04, Last modification date: 2023-12-27)

Primary citation

Suzuki, N.N.,Koizumi, K.,Fukushima, M.,Matsuda, A.,Inagaki, F.
Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase
STRUCTURE, 12:751-764, 2004

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.

PubMed: 15130468
DOI: 10.1016/j.str.2004.02.038

Experimental method

X-RAY DIFFRACTION (2.6 Å)