DNA methyltransferase

Function

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.

Methylguanine DNMT repairs the DNA lesion O⁶-methylguanine to guanine.^[1]
Methylcytosine DNMT methylates the 5 position of cytosine. ^[2]
Methyladenine DNMT methylates the 6 position of adenine. ^[3]
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^[4].

Relevance

DNMT inhibitors are being tested in cancer therapy.

Disease

The human ICF disorder is caused by mutations in DNMT 3B.

Structural highlights

The .

3D Structures of DNA methyltransferase3D Structures of DNA methyltransferase

Updated on 30-April-2018

Methylguanine DNMT
- 1sfe – O6-methylguanine DNMT C terminal – Escherichia coli
- 1qnt, 1eh6, 3llr - hO6-methylguanine DNMT – human
- 1t38 - hO6-methylguanine DNMT (mutant) + DNA
- 1t39, 1yfh - hO6-methylguanine DNMT + DNA
- 1eh7 - hO6-methylguanine DNMT methylated
- 1eh8 - hO6-methylguanine DNMT benzylated
- 1mgt - O6-methylguanine DNMT – Thermococcus kodakarensis
- 1wrj - O6-methylguanine DNMT - Sulfolobus tokodaii
- 2g7h - O6-methylguanine DNMT – Methanocaldococcus jannaschii
- 2kif, 2kim - O6-methylguanine DNMT – Vibrio parahaemolyticus - NMR
- 4bhb, 4bhc, 4wxd, 4wxc - MtO6-methylguanine DNMT (mutant) – Mycobacterium tuberculosis
- 4wx9 - MtO6-methylguanine DNMT (mutant) + modified DNA
- 4zyg, 4zye - O6-methylguanine DNMT – Sulfolobus solfataricus
- 5llq, 4zyh - O6-methylguanine DNMT (mutant)
- 4zyd - O6-methylguanine DNMT (mutant) + modified DNA
Methylcytosine DNMT
- 2qrv - h-cytosine DNMT
- 3epz - h-cytosine DNMT replecation foci-targeting sequence
- 3flg - h-cytosine DNMT ADD domain
- 3a1a - h-cytosine DNMT PWWP domain
- 1g55 - h-cytosine DNMT2 (mutant)
- 3qkj - h-cytosine DNMT 3β
- 2uyc, 2uyh, 2uz4 - Hh-cytosine DNMT (mutant) + DNA + SAH
- 3a1b, 4qbq - h-cytosine DNMT ADD domain + histone H3
- 4qbr, 4qbs - h-cytosine DNMT ADD domain (mutant) + histone H3
- 5ciu - h-cytosine DNMT residues 206-355 + histone H3.2
- 4yoc - h-cytosine DNMT residues 600-1600 + ubiquitin carboxyl-terminal hydrolase 7
- 4z97, 4z96 - h-cytosine DNMT residues 1097-1129 + ubiquitin carboxyl-terminal hydrolase 7
- 5ydr - h-cytosine DNMT RFTS domain residues 351-599 + ubiquitin
- 5wvo - h-cytosine DNMT RFTS domain + ubiquitin + histone H3.1
- 4wxx - h-cytosine DNMT residues 351-1600 + SAH
- 4u7p - h-cytosine DNMT 3A residues 455-912 + h-cytosine DNMT 3-like residues 178-379 + SAH
- 6f57, 5yx2 - h-cytosine DNMT 3A residues 628-912 + h-cytosine DNMT 3-like residues 178-379 + DNA + SAH + pyrimidine derivative
- 6f57 - h-cytosine DNMT 3A residues 439-723 + h-cytosine DNMT 3-like residues 178-379 + DNA + SAH + pyrimidine derivative
- 4u7t - h-cytosine DNMT 3A residues 455-912 + h-cytosine DNMT 3-like residues 178-379 + histone 3.3 + SAH
- 3av4, 1khc - m-cytosine DNMT – mouse
- 5wy1 - m-cytosine DNMT (mutant)
- 5guv, 5gut - m-cytosine DNMT residues 731-1600 (mutant)
- 3pt6, 3pt9, 4da4 – m-cytosine DNMT + DNA

- 3av5 - m-cytosine DNMT + SAH
- 3av6 - m-cytosine DNMT + SAM
- 3swr - h-cytosine DNMT + sinefungin
- 1boo - cytosine DNMT (mutant) – Proteus vulgaris
- 3qv2 - cytosine DNMT + SAH – Entamoeba histolytica
- 2uyc, 2uyh, 2uz4, 1fjx – Hh-cytosine DNMT (mutant) + DNA + SAH - Haemophilus haemolyticus
- 2c7o, 2c7p, 2c7q, 2c7r, 3pta – Hh-cytosine DNMT + DNA + S-adenonosyl cysteine
- 1hmy – Hh-cytosine Haeiii DNMT + SAM
- 1m0e - Hh-cytosine DNMT (mutant) + DNA + inhibitor
- 2i9k - Hh-cytosine DNMT (mutant) + DNA
- 2hr1 - Hh-cytosine DNMT + DNA + ADOHCY
- 2z6q, 2z6u, 2zcj - Hh-cytosine DNMT (mutant) + DNA + ADOHCY
- 1svu - Hh-cytosine DNMT (mutant)
- 4fsx – c-cytosine DNMT + SAH – corn
- 4ft2, 4ft4 – c-cytosine DNMT + histone H3 peptide
- 4h0n - cytosine DNMT (mutant) – Spodoptera frugiperda
Methyladenine DNMT
- 1nw5 – RsN6-adenine DNMT + SAM – Rhodobacter sphaeroides
- 1nw6 - RsN6-adenine DNMT + sinefungin
- 1nw7 - RsN6-adenine DNMT + SAH
- 1nw8 - RsN6-adenine DNMT (mutant)
- 5hek - HpN6-adenine DNMT – Helicobacter pylori
- 5hfj - HpN6-adenine DNMT + SAM
- 2ibs, 2ibt, 2ih2, 2ih4, 2ih5, 2np6, 2np7, 1g38 - Ta-adenine DNMT Taqi + DNA + cofactor analog – Thermus aquaticus
- 1aqi – Ta-adenine DNMT Taqi + SAH
- 1aqj – Ta-adenine DNMT Taqi + sinefungin
- 2adm - Ta-adenine DNMT Taqi + SAM
- 1g60 - adenine DNMT + SAM – Moraxella bovis
- 4rtj, 4rtl, 4rto - Ec-adenine DNMT + DNA + sinefungin
- 4rtk - Ec-adenine DNMT + DNA + SAH
- 4gbe - Ec-adenine DNMT + SAH
- 4gol, 4gom, 4gon, 4goo - Ec-adenine DNMT + SAM derivative
- 4rtm, 4rtp, 4rtr, 4rts - Ec-adenine DNMT + DNA + AdoMet
- 4rtn, 4rtq - Ec-adenine DNMT + DNA + AdoHcy
HhaI DNA methyltransferase
- 1fjx, 2hmy – HhHDMT + SAM – Haemophilus haemolyticus
- 1svu – HhHDMT (mutant) + SAH
- 1hmy, 1mht, 3mht, 4mht, 5mht, 7mht, 8mht, 2hr1, 3eeo – HhHDMT + DNA + SAH
- 2i9k, 2z6a, 2z6u, 2zcj – HhHDMT (mutant) + DNA + SAH
- 6mht – HhHDMT + DNA + SAH + thiodeoxycytidine
- 9mht – HhHDMT + DNA + SAH + abasic dideoxyribose
- 1skm – HhHDMT + DNA + SAH + bicyclohexane
- 10mh – HhHDMT + DNA + SAH + dihydroazacytosine
- 1m0e – HhHDMT + DNA + SAH + zebularine
- 2c7o, 2c7p, 2c7q – HhHDMT + DNA + SAH + methyl cytosine + aminopurine
- 2c7r – HhHDMT (mutant) + DNA + SAH + methyl cytosine + aminopurine
- 2z6q – HhHDMT (mutant) + DNA + SAH + deoxycytidine
- 2uyc, 2uyh, 2uz4 – HhHDMT (mutant) + DNA + SAH + methyl cytosine
DNA methyltransferase
- 4onj – tHDMT catalytic domain + sinefungin – tobacco
- 4onq – tHDMT catalytic domain (mutant) + sinefungin

ReferencesReferences

↑ 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
↑ 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
↑ 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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[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

[1]

[2]

[3]

[4]