1m0e
From Proteopedia
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ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE
Overview
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.
About this Structure
1M0E is a Single protein structure of sequence from Haemophilus haemolyticus with SAH as ligand. Active as Deleted entry, with EC number 2.1.1.73 Full crystallographic information is available from OCA.
Reference
Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases., Zhou L, Cheng X, Connolly BA, Dickman MJ, Hurd PJ, Hornby DP, J Mol Biol. 2002 Aug 23;321(4):591-9. PMID:12206775
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