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.   
'''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 November 2011''
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
== 3D Structures of DNA methyltransferase ==
 
[[DNA methyltransferase 3D structures]]
[[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)
 
[[3av4]], [[1khc]] - m-cytosine DNMT – mouse
 
[[2c7o]], [[2c7p]], [[2c7q]], [[2c7r]], [[3pta]] – Hh-cytosine DNMT + DNA + S-adenonosyl cysteine
 
[[2uyc]], [[2uyh]], [[2uz4]] - Hh-cytosine DNMT (mutant) + DNA + S-adenonosyl cysteine
 
[[3a1b]] - h-cytosine DNMT ADD domain + histone H3
 
[[3pt6]], [[3pt9]] – m-cytosine DNMT + DNA
[[3av5]] - m-cytosine DNMT + S-adenonosyl cysteine
 
[[3av6]] - m-cytosine DNMT + SAM
 
[[3swr]] - h-cytosine DNMT + sinefungin
 
[[1boo]] - cytosine DNMT (mutant) – ''Proteus vulgaris''
 
[[1fjx]] – HhDNMT (mutant) + DNA + S-adenonosyl cysteine - ''Haemophilus haemolyticus''
 
[[1hmy]] – HhHaeiii DNMT + S-adenonosyl methionine
 
 
[[1m0e]] - HhDNMT (mutant) + DNA + inhibitor
 
[[2i9k]] - HhDNMT (mutant) + DNA
 
[[2hr1]] - HhDNMT + DNA + ADOHCY
 
[[2z6q]], [[2z6u]], [[2zcj]] - HhDNMT (mutant) + DNA + ADOHCY
 
[[1svu]] - HhDNMT (mutant)
 
===Methyladenine DNMT===
 
[[1nw5]] – RsN6-adenine DNMT + SAM – ''Rhodobacter sphaeroides''
 
[[1nw6]] - RsN6-adenine DNMT + sinefungin
 
[[1nw8]] - RsN6-adenine DNMT (mutant)
 
[[2ibs]], [[2ibt]], [[2ih2]], [[2ih4]], [[2ih5]], [[2np6]], [[2np7]] - adenine DNMT Taqi + DNA + cofactor analog – ''Thermus aquaticus''


[[1nw7]] - RsN6-adenine DNMT + S-adenonosyl cysteine
</StructureSection>


== References ==
<references/>




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

Michal Harel, Alexander Berchansky