1m0e
From Proteopedia
(Difference between revisions)
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<StructureSection load='1m0e' size='340' side='right'caption='[[1m0e]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='1m0e' size='340' side='right'caption='[[1m0e]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[1m0e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <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> |
- | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
- | <tr id=' | + | <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='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 == | ||
- | + | [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> | ||
- | <div style="background-color:#fffaf0;"> | ||
- | == Publication Abstract from PubMed == | ||
- | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
- | </div> | ||
- | <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]] | ||
- | == References == | ||
- | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
- | [[Category: | + | [[Category: Haemophilus haemolyticus]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
- | [[Category: Cheng | + | [[Category: Cheng X]] |
- | [[Category: Connolly | + | [[Category: Connolly BA]] |
- | [[Category: Dickman | + | [[Category: Dickman MJ]] |
- | [[Category: Hornby | + | [[Category: Hornby DP]] |
- | [[Category: Hurd | + | [[Category: Hurd PJ]] |
- | [[Category: Zhou | + | [[Category: Zhou L]] |
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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
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