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1m0e

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[[Image:1m0e.gif|left|200px]]
[[Image:1m0e.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1m0e |SIZE=350|CAPTION= <scene name='initialview01'>1m0e</scene>, resolution 2.50&Aring;
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The line below this paragraph, containing "STRUCTURE_1m0e", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=Z:ZEBULARINE'>Z</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_1m0e| PDB=1m0e | SCENE= }}
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|RELATEDENTRY=[[9mht|9MHT]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m0e OCA], [http://www.ebi.ac.uk/pdbsum/1m0e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1m0e RCSB]</span>
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}}
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'''ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE'''
'''ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE'''
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[[Category: Hurd, P J.]]
[[Category: Hurd, P J.]]
[[Category: Zhou, L.]]
[[Category: Zhou, L.]]
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[[Category: mechanism based dna methylation inhibitor]]
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[[Category: Mechanism based dna methylation inhibitor]]
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[[Category: protein-dna covalent complex]]
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[[Category: Protein-dna covalent complex]]
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[[Category: zebularine]]
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[[Category: Zebularine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:28:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:09:36 2008''
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Revision as of 21:28, 2 May 2008

Image:1m0e.gif

Template:STRUCTURE 1m0e

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. 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 Page seeded by OCA on Sat May 3 00:28:56 2008

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