1P61

Structure of human dCK complexed with 2'-Deoxycytidine and ADP, P 43 21 2 space group

1P61 の概要

• エントリーDOI: 10.2210/pdb1p61/pdb
• 関連するPDBエントリー: 1P5Z 1P60 1P62
• 分子名称: Deoxycytidine kinase, ADENOSINE-5'-DIPHOSPHATE, 2'-DEOXYCYTIDINE, ... (4 entities in total)
• 機能のキーワード: nucleoside kinase, p-loop, deoxycytidine, 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: 1
• 化学式量合計: 31489.20

構造登録者

Sabini, E.,Ort, S.,Monnerjahn, C.,Konrad, M.,Lavie, A. (登録日: 2003-04-28, 公開日: 2003-07-01, 最終更新日: 2024-02-14)

主引用文献

Sabini, E.,Ort, S.,Monnerjahn, C.,Konrad, M.,Lavie, A.
Structure of human dCK suggests strategies to improve anticancer and antiviral therapy
Nat.Struct.Biol., 10:513-519, 2003

PubMed Abstract: Human deoxycytidine kinase (dCK) phosphorylates the natural deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA) and is an essential enzyme for the phosphorylation of numerous nucleoside analog prodrugs routinely used in cancer and antiviral chemotherapy. For many of these compounds, the phosphorylation step catalyzed by dCK is the rate-limiting step in their overall activation pathway. To determine the factors that limit the phosphorylation efficiency of the prodrug, we solved the crystal structure of dCK to a resolution of 1.6 A in complex with its physiological substrate deoxycytidine and with the prodrugs AraC and gemcitabine. The structures reveal the determinants of dCK substrate specificity. Especially relevant to new prodrug development is the interaction between Arg128 and the hydrogen-bond acceptor at the sugar 2'-arabinosyl position of AraC and gemcitabine. On the basis of the structures, we designed a catalytically superior dCK variant that could be used in suicide gene-therapy applications.

PubMed: 12808445
DOI: 10.1038/nsb942

実験手法

X-RAY DIFFRACTION (2.21 Å)