1m0e

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{{STRUCTURE_1m0e| PDB=1m0e | SCENE= }}
{{STRUCTURE_1m0e| PDB=1m0e | SCENE= }}
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'''ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE'''
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===ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE===
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==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Protein-dna covalent complex]]
[[Category: Protein-dna covalent complex]]
[[Category: Zebularine]]
[[Category: Zebularine]]
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Revision as of 19:56, 2 July 2008

Image:1m0e.png

Template:STRUCTURE 1m0e

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

Template:ABSTRACT PUBMED 12206775

About this Structure

1M0E is a Single protein structure of sequence from Haemophilus haemolyticus. 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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