Histone methyltransferase

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{{STRUCTURE_3s7j| PDB=3s7j | SIZE=400| SCENE= |right|CAPTION=Human histone-lysine N-methyltrasferase Smyd2 complex with S-adenosyl methionine, [[3s7j]] }}
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<StructureSection load='' size='350' side='right' caption='Human histone-lysine N-methyltrasferase (magenta) complex with methylated lysine histone H3 peptide (green) and S-adenosyl homocysteine (SAH) (PDB entry [[1o9s]])' scene='46/467278/Cv/1'>
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'''Histone methyltransferase''' (HMT) are '''histone-lysine N-methyltransferase''' (KHMT) and '''histone-arginine N-methyltransferase''' (RHMT) which catalyzes the transfer of methyl groups to lysine and arginine residues of histones. HMT use S-adenosyl methionine (SAM) or S-adenosyl homocysteine (SAH) as the methyl donor. KHMT can be SET domain-containing or non-SET domain-containing. The SET domain contains the catalytic core of KHMT and targets the lysine tail region of KHMT. CxxC domain is a zinc finger domain.
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== Function ==
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'''Histone methyltransferase''' (HMT) are '''histone-lysine N-methyltransferase''' (KHMT) and '''histone-arginine N-methyltransferase''' (RHMT) which catalyzes the transfer of methyl groups to lysine and arginine residues of histones<ref>PMID:15248813</ref>. HMT use S-adenosyl methionine (SAM) or S-adenosyl homocysteine (SAH) as the methyl donor. KHMT can be SET domain-containing or non-SET domain-containing. The SET domain contains the catalytic core of KHMT and targets the lysine tail region of KHMT. CxxC domain is a zinc finger domain.
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For SET7/9 see [[Histone Lysine Methyltransferase SET7/9]].
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== 3D Structures of histone methyltransferase ==
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== Relevance ==
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Inhibitors of the histone-lysine N-methyltransferase SMYD2 which represses the tumor-suppressing activities of p53 are studied as cancer therapy drugs<ref>PMID:21782458</ref>.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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== Disease ==
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{{#tree:id=OrganizedByTopic|openlevels=0|
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Aberrant HMT plays a role in cancer, intellectual disability syndromes and regulation of tissue aging<ref>PMID:22473383</ref>.
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*DOT1L histone methyltransferase
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== Structural highlights ==
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Human <scene name='46/467278/Cv/6'>KHMT binds SAH in the peptide binding groove with the histone H3 peptide assuming an extended conformation and the methylated lysine</scene> inserted in a hydrophobic environment<ref>PMID:12540855</ref>. Water molecules shown as red spheres
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**[[1nw3]] – hHMT DOT1L – human
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== 3D Structures of histone methyltransferase ==
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[[Histone methyltransferase 3D structures]]
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*Euchromatic histone methyltransferase
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</StructureSection>
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**[[2igq]] – hHMT-1 C terminal
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*Histone-lysine N-methyltransferase
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**[[2j8a]] – KHMT SET1 RRM domain – yeast
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**[[3s8s]] – hKHMT SETD1A RRM domain<br />
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**[[2mdc]], [[2mdj]] - hKHMT SETD2 WW domain - NMR<br />
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**[[2mdi]] - hKHMT SETD2 WW domain (mutant) - NMR<br />
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**[[2r3a]] – hKHMT Suv39H2<br />
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**[[3rq4]] - hKHMT Suv420H2<br />
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**[[3s8p]] - hKHMT Suv420H1<br />
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**[[3mts]] - hKHMT Suv39H1 chromo domain<br />
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**[[1h3i]] - hKHMT SET7/9 residues 52-344<br />
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**[[2o8j]] - hKHMT H3K9 residues 913-1193<br />
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**[[2lv9]] - hKHMT Mll5 residues 109-188 - NMR<br />
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**[[2kyu]] - hKHMT Mll Phd3 finger – NMR<br />
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**[[4gnd]] - hKHMT Nsd3 Phd5-C5HCH<br />
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**[[4rxj]] - hKHMT Nsd3 residues 953-1064<br />
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**[[4yz8]] - hKHMT Nsd3 residues 1054-1285<br />
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**[[3lqh]] - hKHMT Mll Phd bromodomain<br />
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**[[3b7b]] - hKHMT ankyrin repeat domains 2-7<br />
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**[[3bo5]] – hKHMT Setmar methyltransferase domain <br />
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**[[3k9j]], [[3k9k]] – hKHMT Setmar transposable domain (mutant)<br />
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**[[3dlm]] - hKHMT Setmdb1 Tudor domain <br />
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**[[3n71]] - hKHMT Smyd1<br />
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**[[3rsn]], [[3s32]] – hKHMT Ash2 N terminal<br />
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**[[3toj]] – hKHMT Ash2 Spry domain<br />
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**[[4ijd]] – hKHMT Prdm9<br />
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**[[4mi0]] – hKHMT Ezh2<br />
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**[[4mi5]] – hKHMT Ezh2 SET domain<br />
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**[[1ml9]] – NcKHMT Dim-5 – ''Neurospora crassa''<br />
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**[[1n3j]] – PvKHMT – Paramecium bursaria chlorella virus<br />
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**[[1u2z]] – yKHMT C terminal<br />
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**[[2l7p]] – AtKHMT Ashh2 CW domain – ''Arabidopsis thaliana'' - NMR<br />
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**[[2lxe]] – AtKHMT Suvr4 SET31 - NMR<br />
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*Histone-lysine N-methyltransferase binary complexes
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**[[2kkf]] – hKHMT Hrx CxxC domain +_DNA – NMR<br />
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**[[4nw3]] – hKHMT Mll CxxC domain + DNA <br />
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**[[4pzi]] – hKHMT CxxC domain + DNA <br />
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**[[3q0b]], [[3q0c]], [[3q0d]], [[3q0f]] – hKHMT SRA domain +_DNA <br />
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**[[3qow]] – hKHMT + SAM <br />
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**[[4fmu]] – hKHMT SETD2 + inhibitor <br />
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**[[4h12]] – hKHMT SETD2 + SAH <br />
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**[[3smt]] – hKHMT SETD3 + SAM <br />
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**[[4bup]], [[3ooi]] – hKHMT SET domain + SAM <br />
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**[[3qox]], [[3sx0]] – hKHMT + SAH <br />
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**[[3sr4]], [[3uwp]], [[4ek9]], [[4ekg]], [[4eki]], [[4eqz]], [[4er0]], [[4er3]], [[4er5]], [[4er6]], [[4er7]], [[4hra]] - hKHMT catalytic domain + inhibitor<br />
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**[[2w5y]] – hKHMT Hrx methyltransferase domain + SAH <br />
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**[[3lqi]], [[3lqj]] - hKHMT Mll Phd bromodomain + H3 peptide<br />
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**[[3f2k]] – hKHMT Setmar SET domain + LYFA peptide<br />
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**[[3sw9]], [[3swc]] – hKHMT SET domain + peptide<br />
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**[[4gne]], [[4gnf]], [[4gng]] - hKHMT Nsd3 Phd5-C5HCH + H3 peptide<br />
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**[[3b95]] - hKHMT ankyrin repeat domain + H3 peptide<br />
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**[[3lqi]], [[3lqj]] - hKHMT Mll1 3rd Phd finger and bromodomain + H3 peptide<br />
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**[[3rib]] – hKHMT Smyd2 + SAH<br />
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**[[3s7j]], [[3tg4]] - hKHMT Smyd2 + SAM<br />
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**[[4wuy]] - hKHMT Smyd2 + inhibitor<br />
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**[[1mt6]] - hKHMT SET7/9 residues 58-337 + SAH<br />
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**[[1n6a]] – hKHMT SET7/9 SET domain + SAM<br />
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**[[1n6c]] – hKHMT SET7/9 residues 70-366 + SAM<br />
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**[[3cbp]] - hKHMT SET7/9 SET domain + sinefungin<br />
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**[[3vuz]], [[3vv0]] - hKHMT SET7/9 SET domain + deoxyadenosine derivative<br />
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**[[4l58]] - hKHMT PHD-type zinc finger domain + H3 peptide<br />
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*Histone-lysine N-methyltransferase ternary complex
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**[[2w5z]] – hKHMT Hrx methyltransferase domain + SAH + histone peptide<br />
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**[[1o9s]] - hKHMT SET7/9 SET domain + SAH + H3 peptide<br />
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**[[2bqz]] - hKHMT SET7 SET domain + SAH + H4 peptide<br />
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**[[3f9w]], [[3f9x]], [[3f9y]], [[3f9z]] - hKHMT SETD8 SET domain + SAH + H4 peptide<br />
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**[[4ij8]] - hKHMT SETD8 + SAM + H3 peptide<br />
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**[[4j7i]], [[4j83]], [[4j8o]], [[4j7f]] - hKHMT SETD7 + SAH + TFIID peptide<br />
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**[[3fpd]], [[3k5k]], [[3mo0]], [[3mo2]], [[3mo5]], [[3rjw]], [[4nvq]] - hKHMT SET domain + SAH + inhibitor<br />
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**[[2rfi]], [[3hna]] - hKHMT H3K9 catalytic domain + SAH + H3 peptide<br />
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**[[1xqh]] - hKHMT SET7/9 SET domain + SAH + p53 peptide<br />
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**[[2f69]], [[3m53]] - hKHMT SET7/9 SZET domain + SAH + TAF10 peptide<br />
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**[[3m54]], [[3m55]], [[3m56]], [[3m57]], [[3m58]], [[3m59]], [[3m5a]] - hKHMT SET7/9 SET domain (mutant) + SAH + TAF10 peptide<br />
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**[[3cbm]] - hKHMT SET7/9 SET domain + SAM + estrogen receptor peptide<br />
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**[[4e47]], [[4jds]], [[4jlg]] - hKHMT SET7/9 SET domain + SAM + inhibitor<br />
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**[[3cbo]] - hKHMT SET7/9 SET domain + SAH + estrogen receptor peptide<br />
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**[[3os5]] - hKHMT SET7/9 SET domain + SAH + DNMT1 peptide<br />
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**[[3qxy]], [[3rc0]] - hKHMT SETD6 SET domain + p65 peptide + SAM<br />
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**[[3s7b]] - hKHMT Smyd2 + SAM + inhibitor<br />
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**[[3s7d]], [[3s7f]], [[3tg5]] - hKHMT Smyd2 + SAH + p53 peptide<br />
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**[[4o6f]] – hKHMT Smyd2 (mutant) + SAH + estrogen receptor peptide<br />
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**[[1zkk]] - hKHMT + SAH + H4 peptide <br />
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**[[4c1q]] - hKHMT SET domain + SAH + H3 peptide <br />
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**[[4i51]] - hKHMT (mutant) + SAH + H3 peptide <br />
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**[[1peg]] - NcKHMT Dim-5 + SAH + H3 peptide<br />
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**[[2g46]] – PvKHMT + SAH + H3 peptide<br />
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**[[4au7]] - mKHMT + SAH + H4 peptide - mouse<br />
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*Histone-arginine N-methyltransferase (Carm1)
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**[[2v74]], [[2v7e]] – mRHMT catalytic domain <br />
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**[[4c03]], [[4c06]], [[4c07]], [[4c08]] – mRHMT 6<br />
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**[[4c04]] – mRHMT 6 + inhibitor<br />
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**[[4c05]] – mRHMT 6 + SAH<br />
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**[[4c4a]] – mRHMT 7 + SAH<br />
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**[[2obq]] – rRHMT N terminal - rat <br />
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**[[3b3g]], [[3b3j]] – rRHMT catalytic domain <br />
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**[[3b3f]] – rRHMT catalytic domain + SAH<br />
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**[[2y1w]], [[2y1x]] – hRHMT 4 catalytic domain + sinefungin + indole inhibitor<br />
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**[[4ikp]] – hRHMT 4 catalytic domain + purine derivative<br />
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**[[4gqb]] – hRHMT 5 + methylsome protein 50 + H4 peptide<br />
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**[[4qqk]] – hRHMT 6 <br />
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**[[4hc4]] – hRHMT 6 (mutant)<br />
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**[[4qpp]] – hRHMT 6 (mutant) + peptide + inhibitor<br />
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}}
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human histone-lysine N-methyltrasferase (magenta) complex with methylated lysine histone H3 peptide (green) and S-adenosyl homocysteine (SAH) (PDB entry 1o9s)

Drag the structure with the mouse to rotate

References

  1. ↑ Trievel RC. Structure and function of histone methyltransferases. Crit Rev Eukaryot Gene Expr. 2004;14(3):147-69. PMID:15248813
  2. ↑ Ferguson AD, Larsen NA, Howard T, Pollard H, Green I, Grande C, Cheung T, Garcia-Arenas R, Cowen S, Wu J, Godin R, Chen H, Keen N. Structural Basis of Substrate Methylation and Inhibition of SMYD2. Structure. 2011 Jul 20. PMID:21782458 doi:10.1016/j.str.2011.06.011
  3. ↑ Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012 Apr 3;13(5):343-57. doi: 10.1038/nrg3173. PMID:22473383 doi:http://dx.doi.org/10.1038/nrg3173
  4. ↑ Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G, Howell S, Taylor IA, Blackburn GM, Gamblin SJ. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature. 2003 Feb 6;421(6923):652-6. Epub 2003 Jan 22. PMID:12540855 doi:10.1038/nature01378

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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