PDBsum entry 1udw

Transferase

PDB id: 1udw

Contents

Protein chain

204 a.a. *

Ligands

CTP ×2

Waters ×76

* Residue conservation analysis

PDB id:

1udw

Name:

Transferase

Title:

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

Structure:

Uridine-cytidine kinase 2. Chain: a, b. Fragment: residues 1-250. Synonym: uridine-cytidine kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.60Å R-factor: 0.210 R-free: 0.251

Authors:

N.N.Suzuki,K.Koizumi,M.Fukushima,A.Matsuda,F.Inagaki

Key ref:

N.N.Suzuki et al. (2004). Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase. Structure, 12, 751-764. PubMed id: 15130468 DOI: 10.1016/j.str.2004.02.038

Date:

07-May-03 Release date: 04-May-04

Protein chains

Q9BZX2  (UCK2_HUMAN) -  Uridine-cytidine kinase 2 from Homo sapiens

Seq: 261 a.a.

Struc: 204 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.48 - uridine/cytidine kinase.
• Reaction:
  1. uridine + ATP = UMP + ADP + H⁺
  2. cytidine + ATP = CMP + ADP + H⁺

uridine (Bound ligand (Het Group name = CTP) matches with 87.50% similarity) + ATP = UMP + ADP + H(+)

cytidine (Bound ligand (Het Group name = CTP) matches with 87.50% similarity) + ATP = CMP + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.str.2004.02.038

Structure 12:751-764 (2004)

PubMed id: 15130468

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

N.N.Suzuki, K.Koizumi, M.Fukushima, A.Matsuda, F.Inagaki.

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.

Selected figure(s)

Figure 3.
Figure 3. Final Annealed F[o] - F[c] Omit Electron Density Map for Ligands Bound to UCK(A) CMP, ADP, and the magnesium ion observed in the CMP-ADP-bound UCK crystal. The map is contoured at 3.5 s and the resolution is 1.8 Å.(B) CTP observed in the CTP-bound UCK crystal. The map is contoured at 4.0 s and the resolution is 2.6 Å.(C) UTP observed in UTP-bound UCK. The map is contoured at 4.0 s and the resolution is 2.6 Å.(D) Cyd and citrate observed in Cyd-bound UCK. The map is contoured at 3.5 s and the resolution is 2.6 Å. This figure was prepared using program O (Jones et al., 1991).

The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 751-764) copyright 2004.

Figure was selected by an automated process.