DNA methyltransferase: Difference between revisions

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Line 64: Line 64:
**[[2uyc]], [[2uyh]], [[2uz4]] - Hh-cytosine DNMT (mutant) + DNA + SAH
**[[2uyc]], [[2uyh]], [[2uz4]] - Hh-cytosine DNMT (mutant) + DNA + SAH


**[[3a1b]] - h-cytosine DNMT ADD domain + histone H3
**[[3a1b]], [[4qbq]] - h-cytosine DNMT ADD domain + histone H3<br />
**[[4qbr]], [[4qbs]] - h-cytosine DNMT ADD domain (mutant) + histone H3<br />
**[[5ciu]] - h-cytosine DNMT residues 206-355 + histone H3.2<br />
**[[4yoc]] - h-cytosine DNMT residues 600-1600 + ubiquitin carboxyl-terminal hydrolase 7<br />
**[[4wxx]] - h-cytosine DNMT residues 351-1600 + SAH<br />
**[[4u7p]] - h-cytosine DNMT 3A residues 455-912 + h-cytosine DNMT 3-like residues 178-379  + SAH<br />
**[[4u7t]] - h-cytosine DNMT 3A residues 455-912 + h-cytosine DNMT 3-like residues 178-379  + histone 3.3 + SAH<br />


**[[3pt6]], [[3pt9]], [[4da4]] – m-cytosine DNMT + DNA
**[[3pt6]], [[3pt9]], [[4da4]] – m-cytosine DNMT + DNA
Line 99: Line 105:
**[[1nw6]] - RsN6-adenine DNMT + sinefungin<br />
**[[1nw6]] - RsN6-adenine DNMT + sinefungin<br />
**[[1nw7]] - RsN6-adenine DNMT + SAH<br />
**[[1nw7]] - RsN6-adenine DNMT + SAH<br />
**[[1nw8]] - RsN6-adenine DNMT (mutant)
**[[1nw8]] - RsN6-adenine DNMT (mutant)<br />
**[[5hek]] - HpN6-adenine DNMT – ''Helicobacter pylori''<br />
**[[5hfj]] - HpN6-adenine DNMT + SAM<br />


**[[2ibs]], [[2ibt]], [[2ih2]], [[2ih4]], [[2ih5]], [[2np6]], [[2np7]], [[1g38]] - Ta-adenine DNMT Taqi + DNA + cofactor analog – ''Thermus aquaticus''<br />
**[[2ibs]], [[2ibt]], [[2ih2]], [[2ih4]], [[2ih5]], [[2np6]], [[2np7]], [[1g38]] - Ta-adenine DNMT Taqi + DNA + cofactor analog – ''Thermus aquaticus''<br />
**[[1aqi]] – Ta-adenine DNMT Taqi + SAH<br />
**[[1aqi]] – Ta-adenine DNMT Taqi + SAH<br />
**[[1aqj]] – Ta-adenine DNMT Taqi + sinefugin<br />
**[[1aqj]] – Ta-adenine DNMT Taqi + sinefungin<br />
**[[2adm]] - Ta-adenine DNMT Taqi + SAM<br />
**[[2adm]] - Ta-adenine DNMT Taqi + SAM<br />
**[[1g60]] - adenine DNMT + SAM – ''Moraxella bovis''
**[[1g60]] - adenine DNMT + SAM – ''Moraxella bovis''<br />
**[[4rtj]], [[4rtl]], [[4rto]] - Ec-adenine DNMT + DNA + sinefungin<br />
**[[4rtk]] - Ec-adenine DNMT + DNA + SAH<br />
**[[4gbe]] - Ec-adenine DNMT + SAH<br />
**[[4gol]], [[4gom]], [[4gon]], [[4goo]] - Ec-adenine DNMT + SAM derivative<br />
**[[4rtm]], [[4rtp]], [[4rtr]], [[4rts]] - Ec-adenine DNMT + DNA + AdoMet<br />
**[[4rtn]], [[4rtq]] - Ec-adenine DNMT + DNA + AdoHcy<br />


*HhaI DNA methyltransferase
*HhaI DNA methyltransferase
Line 122: Line 136:
**[[2z6q]] – HhHDMT (mutant) + DNA + SAH + deoxycytidine  <BR />
**[[2z6q]] – HhHDMT (mutant) + DNA + SAH + deoxycytidine  <BR />
**[[2uyc]], [[2uyh]], [[2uz4]] – HhHDMT (mutant) + DNA + SAH + methyl cytosine <BR />
**[[2uyc]], [[2uyh]], [[2uz4]] – HhHDMT (mutant) + DNA + SAH + methyl cytosine <BR />
*DNA methyltransferase
**[[4onj]] – tHDMT catalytic domain + sinefungin – tobacco <BR />
**[[4onq]] – tHDMT catalytic domain (mutant) + sinefungin <BR />


}}
}}

Revision as of 13:24, 24 April 2017

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 .

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

Drag the structure with the mouse to rotate

3D Structures of DNA methyltransferase3D Structures of DNA methyltransferase

Updated on 24-April-2017

    • 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

  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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