2A30

Crystal structure of human deoxycytidine kinase in complex with deoxycytidine

2A30 の概要

• エントリーDOI: 10.2210/pdb2a30/pdb
• 関連するPDBエントリー: 2A2Z
• 分子名称: Deoxycytidine kinase, CALCIUM ION, 2'-DEOXYCYTIDINE, ... (4 entities in total)
• 機能のキーワード: nucleoside kinase, 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: 4
• 化学式量合計: 117545.04

構造登録者

Godsey, M.H.,Ort, S.,Sabini, E.,Konrad, M.,Lavie, A. (登録日: 2005-06-23, 公開日: 2006-01-17, 最終更新日: 2023-08-23)

主引用文献

Godsey, M.H.,Ort, S.,Sabini, E.,Konrad, M.,Lavie, A.
Structural basis for the preference of UTP over ATP in human deoxycytidine kinase: illuminating the role of main-chain reorganization.
Biochemistry, 45:452-461, 2006

PubMed Abstract: Human deoxycytidine kinase (dCK) uses nucleoside triphosphates to phosphorylate several clinically important prodrugs in addition to its natural substrates. Although UTP is the preferred phosphoryl donor for this reaction, our previous studies reported dCK structures solely containing ADP in the phosphoryl donor binding site. To determine the molecular basis of the kinetically observed phosphoryl donor preference, we solved crystal structures of a dCK variant lacking a flexible insert (residues 65-79) but having similar catalytic properties as wild type, in complex with deoxycytidine (dC) and UDP, and in the presence of dC but the absence of UDP or ADP. These structures reveal major changes in the donor base binding loop (residues 240-247) between the UDP-bound and ADP-bound forms, involving significant main-chain rearrangement. This loop is disordered in the dCK-dC structure, which lacks a ligand at the phosphoryl donor site. In comparison with the ADP-bound form, in the presence of UDP this loop is shifted inward to make closer contact to the smaller uracil base. These structures illuminate the phosphoryl donor binding and preference mechanisms of dCK.

PubMed: 16401075
DOI: 10.1021/bi0518646

実験手法

X-RAY DIFFRACTION (3.02 Å)