DNA methyltransferase

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'''DNA methyltransferase''' (DNMT) catalyzes the transfer of methyl group to DNA. DNMT uses S-adenosyl methionine (SAM) as the methyl donor.
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<StructureSection load='1nw5' size='350' side='right' caption='Adenine DNMT complex with SAM and Cl- ion (PDB code [[1nw5]]).' scene='46/467277/Cv/1'>
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__TOC__
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== Function ==
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===Methylguanine DNMT===
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'''DNA methyltransferase''' (DNMT) catalyzes the transfer of methyl group to DNA. Methylation is essential for gene expression. DNMT uses S-adenosyl methionine (SAM) as the methyl donor. The SAM analog S-adenosyl homocysteine (SAH) is a powerful inhibitor of DNMT.
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[[1sfe]] – O6-methylguanine DNMT C terminal – ''Escherichia coli''
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*'''Methylguanine DNMT''' repairs the DNA lesion O<sup>6</sup>-methylguanine to guanine.<ref>PMID:17485253</ref><br />
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*'''Methylcytosine DNMT''' methylates the 5 position of cytosine. <ref>PMID:8127644</ref><br />
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*'''Methyladenine DNMT''' methylates the 6 position of adenine. <ref>PMID:12732637</ref><br />
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*'''HhaI DNA methyltransferase''' (HDMT), a DNMT from ''Haemophilus haemolyticus'' recognizes the 5’-GCGC-3’ DNA sequence and methylates the first cytosine to convert it to 5-methylcytosine. The SAM serves as the methyl donor in the reaction and is converted to to S-adenosyl-L-homocysteine (SAH) by the reaction<ref>PMID:12139442</ref>.
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[[1qnt]], [[1eh6]], [[3llr]] - hO6-methylguanine DNMT – human
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== Relevance ==
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[[1t38]] - hO6-methylguanine DNMT (mutant) + DNA
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DNMT inhibitors are being tested in cancer therapy.
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[[1t39]], [[1yfh]] - hO6-methylguanine DNMT + DNA
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== Disease ==
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[[1eh7]] - hO6-methylguanine DNMT methylated
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The human ICF disorder is caused by mutations in DNMT 3B.
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[[1eh8]] - hO6-methylguanine DNMT benzylated
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== Structural highlights ==
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The <scene name='46/467277/Cv/8'>active site of methyladenine DNMT contains the methyl donor SAM</scene>.
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[[1wrj]] - O6-methylguanine DNMT - ''Sulfolobus tokodaii''
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== 3D Structures of DNA methyltransferase ==
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[[DNA methyltransferase 3D structures]]
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[[2g7h]] - O6-methylguanine DNMT – ''Methanocaldococcus jannaschii''
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</StructureSection>
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[[2kif]], [[2kim]] - O6-methylguanine DNMT – ''Vibrio parahaemolyticus'' - NMR
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== References ==
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<references/>
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===Methylcytosine DNMT===
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[[Category:Topic Page]]
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[[2qrv]] - h-cytosine DNMT
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[[3epz]] - h-cytosine DNMT replecation foci-targeting sequence
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[[3flg]] - h-cytosine DNMT ADD domain
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[[3a1a]] - h-cytosine DNMT PWWP domain
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[[3av4]] - m-cytosine DNMT – mouse
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[[2c7o]], [[2c7p]], [[2c7q]], [[2c7r]], [[3pta]] – Hh-cytosine DNMT + DNA + S-adenonosyl cysteine
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[[2uyc]], [[2uyh]], [[2uz4]] - Hh-cytosine DNMT (mutant) + DNA + S-adenonosyl cysteine
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[[3a1b]] - h-cytosine DNMT ADD domain + histone H3
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[[3pt6]], [[3pt9]] – m-cytosine DNMT + DNA
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[[3av5]] - m-cytosine DNMT + S-adenonosyl cysteine
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[[3av6]] - m-cytosine DNMT + SAM
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[[3swr]] - h-cytosine DNMT + sinefungin
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[[1fjx]] – HhDNMT (mutant) + DNA + S-adenonosyl cysteine - Haemophilus haemolyticus
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===Methyladenine DNMT===
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[[1nw5]] – RsN6-adenine DNMT + SAM – ''Rhodobacter sphaeroides''
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[[1nw6]] - RsN6-adenine DNMT + sinefungin
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[[1nw7]] - RsN6-adenine DNMT + S-adenonosyl cysteine
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Current revision

Adenine DNMT complex with SAM and Cl- ion (PDB code 1nw5).

Drag the structure with the mouse to rotate

References

  1. Kaina B, Christmann M, Naumann S, Roos WP. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst). 2007 Aug 1;6(8):1079-99. Epub 2007 May 7. PMID:17485253 doi:http://dx.doi.org/10.1016/j.dnarep.2007.03.008
  2. Kumar S, Cheng X, Klimasauskas S, Mi S, Posfai J, Roberts RJ, Wilson GG. The DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 1994 Jan 11;22(1):1-10. PMID:8127644
  3. Thomas CB, Scavetta RD, Gumport RI, Churchill ME. Structures of liganded and unliganded RsrI N6-adenine DNA methyltransferase: a distinct orientation for active cofactor binding. J Biol Chem. 2003 Jul 11;278(28):26094-101. Epub 2003 May 4. PMID:12732637 doi:http://dx.doi.org/10.1074/jbc.M303751200
  4. Sankpal UT, Rao DN. Structure, function, and mechanism of HhaI DNA methyltransferases. Crit Rev Biochem Mol Biol. 2002;37(3):167-97. PMID:12139442 doi:http://dx.doi.org/10.1080/10409230290771492

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Michal Harel, Alexander Berchansky

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