1m0e: Difference between revisions
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New page: left|200px<br /><applet load="1m0e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m0e, resolution 2.50Å" /> '''ZEBULARINE: A NOVEL ... |
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[[Image:1m0e.gif|left|200px]]<br /><applet load="1m0e" size=" | [[Image:1m0e.gif|left|200px]]<br /><applet load="1m0e" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1m0e, resolution 2.50Å" /> | caption="1m0e, resolution 2.50Å" /> | ||
'''ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE'''<br /> | '''ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE'''<br /> | ||
==Overview== | ==Overview== | ||
Mechanism-based inhibitors of enzymes, which mimic reactive intermediates | 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== | ==About this Structure== | ||
1M0E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Haemophilus_haemolyticus Haemophilus haemolyticus] with SAH as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Deleted_entry Deleted entry], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.73 2.1.1.73] Full crystallographic information is available from [http:// | 1M0E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Haemophilus_haemolyticus Haemophilus haemolyticus] with <scene name='pdbligand=SAH:'>SAH</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Deleted_entry Deleted entry], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.73 2.1.1.73] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M0E OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cheng, X.]] | [[Category: Cheng, X.]] | ||
[[Category: Connolly, B | [[Category: Connolly, B A.]] | ||
[[Category: Dickman, M | [[Category: Dickman, M J.]] | ||
[[Category: Hornby, D | [[Category: Hornby, D P.]] | ||
[[Category: Hurd, P | [[Category: Hurd, P J.]] | ||
[[Category: Zhou, L.]] | [[Category: Zhou, L.]] | ||
[[Category: SAH]] | [[Category: SAH]] | ||
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[[Category: zebularine]] | [[Category: zebularine]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:50:09 2008'' | ||
