3QEJ

S74E-dCK mutant in complex with UDP

3QEJ の概要

• エントリーDOI: 10.2210/pdb3qej/pdb
• 分子名称: Deoxycytidine kinase, URIDINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: alpha/beta, phosphoryl transfer, atp binding, phosphorylation, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P27707
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66037.42

構造登録者

Hazra, S.,Lavie, A. (登録日: 2011-01-20, 公開日: 2011-03-16, 最終更新日: 2024-02-21)

主引用文献

Hazra, S.,Szewczak, A.,Ort, S.,Konrad, M.,Lavie, A.
Post-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release.
Biochemistry, 50:2870-2880, 2011

PubMed Abstract: Deoxycytidine kinase (dCK) uses either ATP or UTP as a phosphoryl donor to catalyze the phosphorylation of nucleoside acceptors. The kinetic properties of human dCK are modulated in vivo by phosphorylation of serine 74. This residue is a part of the insert region and is distant from the active site. Replacing the serine with a glutamic acid (S74E variant) can mimic phosphorylation of Ser74. To understand how phosphorylation affects the catalytic properties of dCK, we examined the S74E variant of dCK both structurally and kinetically. We observe that the presence of a glutamic acid at position 74 favors the adoption by the enzyme of the open conformation. Glu74 stabilizes the open conformation by directly interacting with the indole side chain of Trp58, a residue that is in the proximity of the base of the nucleoside substrate. The open dCK conformation is competent for the binding of nucleoside but not for phosphoryl transfer. In contrast, the closed conformation is competent for phosphoryl transfer but not for product release. Thus, dCK must make the transition between the open and closed states during the catalytic cycle. We propose a reaction scheme for dCK that incorporates the transition between the open and closed states, and this serves to rationalize the observed kinetic differences between wild-type dCK and the S74E variant.

PubMed: 21351740
DOI: 10.1021/bi2001032

実験手法

X-RAY DIFFRACTION (2.49 Å)