1M0E

ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE

1M0E の概要

• エントリーDOI: 10.2210/pdb1m0e/pdb
• 関連するPDBエントリー: 9MHT
• 分子名称: 5'-D(P*CP*CP*AP*TP*GP*CP*GP*CP*TP*GP*AP*C)-3', 5'-D(P*GP*TP*CP*AP*GP*(Z)P*GP*CP*AP*TP*GP*G)-3', Modification methylase HhaI, ... (5 entities in total)
• 機能のキーワード: protein-dna covalent complex, mechanism based dna methylation inhibitors, zebularine, transferase-dna complex, transferase/dna
• 由来する生物種: Haemophilus haemolyticus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44738.39

構造登録者

Zhou, L.,Cheng, X.,Connolly, B.A.,Dickman, M.J.,Hurd, P.J.,Hornby, D.P. (登録日: 2002-06-12, 公開日: 2002-09-18, 最終更新日: 2024-10-30)

主引用文献

Zhou, L.,Cheng, X.,Connolly, B.A.,Dickman, M.J.,Hurd, P.J.,Hornby, D.P.
ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASES
J.MOL.BIOL., 321:591-599, 2002

PubMed Abstract: Mechanism-based inhibitors of enzymes, which mimic reactive intermediates in the reaction pathway, have been deployed extensively in the analysis of metabolic pathways and as candidate drugs. The inhibition of cytosine-[C5]-specific DNA methyltransferases (C5 MTases) by oligodeoxynucleotides containing 5-azadeoxycytidine (AzadC) and 5-fluorodeoxycytidine (FdC) provides a well-documented example of mechanism-based inhibition of enzymes central to nucleic acid metabolism. Here, we describe the interaction between the C5 MTase from Haemophilus haemolyticus (M.HhaI) and an oligodeoxynucleotide duplex containing 2-H pyrimidinone, an analogue often referred to as zebularine and known to give rise to high-affinity complexes with MTases. X-ray crystallography has demonstrated the formation of a covalent bond between M.HhaI and the 2-H pyrimidinone-containing oligodeoxynucleotide. This observation enables a comparison between the mechanisms of action of 2-H pyrimidinone with other mechanism-based inhibitors such as FdC. This novel complex provides a molecular explanation for the mechanism of action of the anti-cancer drug zebularine.

PubMed: 12206775
DOI: 10.1016/S0022-2836(02)00676-9

実験手法

X-RAY DIFFRACTION (2.5 Å)