DNA methyltransferase: Difference between revisions

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{{STRUCTURE_1qnt|  PDB=1qnt  | SIZE=400| SCENE= |right|CAPTION=Human O6-methylguanine DNA methyltransferase, [[1qnt]] }}
<StructureSection load='1nw5' size='350' side='right' caption='Adenine DNMT complex with SAM and Cl- ion (PDB code [[1nw5]]).' scene='46/467277/Cv/1'>
__TOC__
== Function ==


'''DNA methyltransferase''' (DNMT) catalyzes the transfer of methyl group to DNA. DNMT uses S-adenosyl methionine (SAM) as the methyl donor.  The SAM analog S-adenosyl homocysteine (SAH) is a powerful inhibitor of DNMT.
'''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.


{{TOC limit|limit=2}}
*'''Methylguanine DNMT''' repairs the DNA lesion O<sup>6</sup>-methylguanine to guanine.<ref>PMID:17485253</ref><br />
*'''Methylcytosine DNMT''' methylates the 5 position of cytosine.  <ref>PMID:8127644</ref><br />
*'''Methyladenine DNMT''' methylates the 6 position of adenine.  <ref>PMID:12732637</ref><br />
*'''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>. 


== 3D Structures of DNA methyltransferase ==
== Relevance ==  


''Updated June 2012''
DNMT inhibitors are being tested in cancer therapy.


===Methylguanine DNMT===
== Disease ==


[[1sfe]] – O6-methylguanine DNMT C terminal – ''Escherichia coli''
The human ICF disorder is caused by mutations in DNMT 3B.


[[1qnt]], [[1eh6]], [[3llr]] - hO6-methylguanine DNMT – human
== Structural highlights ==


[[1t38]] - hO6-methylguanine DNMT (mutant) + DNA
The <scene name='46/467277/Cv/8'>active site of methyladenine DNMT contains the methyl donor SAM</scene>.
 
[[1t39]], [[1yfh]] - hO6-methylguanine DNMT + DNA
 
[[1eh7]] - hO6-methylguanine DNMT methylated
 
[[1eh8]] - hO6-methylguanine DNMT benzylated
 
 
[[1wrj]] - O6-methylguanine DNMT  - ''Sulfolobus tokodaii''
 
[[2g7h]] - O6-methylguanine DNMT – ''Methanocaldococcus jannaschii''
 
[[2kif]], [[2kim]] - O6-methylguanine DNMT – ''Vibrio parahaemolyticus'' - NMR
 
 
===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)<br />
[[3qkj]] - h-cytosine DNMT 3β<br />
[[3av4]], [[1khc]] - m-cytosine DNMT – mouse
 
[[2uyc]], [[2uyh]], [[2uz4]] - Hh-cytosine DNMT (mutant) + DNA + SAH
 
[[3a1b]] - h-cytosine DNMT ADD domain + histone H3
 
[[3pt6]], [[3pt9]] – 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''<br />
[[3qv2]] - cytosine DNMT + SAH – ''Entamoeba histolytica''<br />
[[2uyc]], [[2uyh]], [[2uz4]], [[1fjx]] – Hh-cytosine DNMT (mutant) + DNA + SAH - ''Haemophilus haemolyticus''<br />
[[2c7o]], [[2c7p]], [[2c7q]], [[2c7r]], [[3pta]] – Hh-cytosine DNMT + DNA + S-adenonosyl cysteine<br />
[[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)
 
===Methyladenine DNMT===
 
[[1nw5]] – RsN6-adenine DNMT + SAM – ''Rhodobacter sphaeroides''
 
[[1nw6]] - RsN6-adenine DNMT + sinefungin<br />
[[1nw7]] - RsN6-adenine DNMT + SAH<br />
[[1nw8]] - RsN6-adenine DNMT (mutant)
 
[[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 />
[[1aqj]] – Ta-adenine DNMT Taqi + sinefugin<br />
[[2adm]] - Ta-adenine DNMT Taqi + SAM<br />
[[1g60]] - adenine DNMT + SAM – ''Moraxella bovis''


== 3D Structures of DNA methyltransferase ==
[[DNA methyltransferase 3D structures]]


</StructureSection>


== References ==
<references/>




[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 11:39, 12 June 2019

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 methyltransferase

DNA methyltransferase 3D structures


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

Drag the structure with the mouse to rotate

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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