DNA methyltransferase

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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]

Relevance

DNMT inhibitors are being tested in cancer therapy.

Disease

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

Structural highlights

The active site of methyladenine DNMT contains the methyl donor SAM.

Adenine DNMT complex with SAM (PDB code 1nw5).

Drag the structure with the mouse to rotate

3D Structures of DNA methyltransferase3D Structures of DNA methyltransferase

Updated on 31-December-2015

    • 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)
    • 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 + sinefugin
    • 2adm - Ta-adenine DNMT Taqi + SAM
    • 1g60 - adenine DNMT + SAM – Moraxella bovis

ReferencesReferences

  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

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

Michal Harel, Alexander Berchansky