1m0e

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<StructureSection load='1m0e' size='340' side='right'caption='[[1m0e]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='1m0e' size='340' side='right'caption='[[1m0e]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1m0e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_x"_pritchett_and_stillman_1919 "bacillus x" pritchett and stillman 1919]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M0E FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1m0e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_haemolyticus Haemophilus haemolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M0E FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=Z:1-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)PYRIMIDIN-2(1H)-ONE'>Z</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=Z:1-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)PYRIMIDIN-2(1H)-ONE'>Z</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[9mht|9mht]]</div></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA_(cytosine-5-)-methyltransferase DNA (cytosine-5-)-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.37 2.1.1.37] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m0e OCA], [https://pdbe.org/1m0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m0e RCSB], [https://www.ebi.ac.uk/pdbsum/1m0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m0e ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m0e OCA], [https://pdbe.org/1m0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m0e RCSB], [https://www.ebi.ac.uk/pdbsum/1m0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m0e ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/MTH1_HAEPH MTH1_HAEPH]] This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease.
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[https://www.uniprot.org/uniprot/MTH1_HAEPH MTH1_HAEPH] This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m0e ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m0e ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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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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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<ref>PMID:12206775</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 1m0e" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillus x pritchett and stillman 1919]]
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[[Category: Haemophilus haemolyticus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Cheng, X]]
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[[Category: Cheng X]]
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[[Category: Connolly, B A]]
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[[Category: Connolly BA]]
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[[Category: Dickman, M J]]
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[[Category: Dickman MJ]]
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[[Category: Hornby, D P]]
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[[Category: Hornby DP]]
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[[Category: Hurd, P J]]
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[[Category: Hurd PJ]]
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[[Category: Zhou, L]]
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[[Category: Zhou L]]
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[[Category: Mechanism based dna methylation inhibitor]]
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[[Category: Protein-dna covalent complex]]
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[[Category: Transferase-dna complex]]
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[[Category: Zebularine]]
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Revision as of 08:29, 10 April 2024

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

PDB ID 1m0e

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