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PDBsum entry 1udw
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis for the specificity, Catalysis, And regulation of human uridine-Cytidine kinase.
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Authors
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N.N.Suzuki,
K.Koizumi,
M.Fukushima,
A.Matsuda,
F.Inagaki.
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Ref.
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Structure, 2004,
12,
751-764.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
751-764)
copyright 2004.
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Secondary reference #1
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Title
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Crystallization and preliminary X-Ray analysis of human uridine-Cytidine kinase 2.
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Authors
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N.N.Suzuki,
K.Koizumi,
M.Fukushima,
A.Matsuda,
F.Inagaki.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2003,
59,
1477-1478.
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PubMed id
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