Histone methyltransferase: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
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
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
== 3D Structures of histone methyltransferase ==
[[Histone methyltransferase 3D structures]]
</StructureSection>
</StructureSection>


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*Histone-lysine N-methyltransferase
*Histone-lysine N-methyltransferase
**[[2j8a]] – KHMT SET1 RRM domain – yeast


**[[3s8s]] – hKHMT SETD1A RRM domain<br />
**[[3s8s]] – hKHMT SETD1A RRM domain<br />
Line 47: Line 49:
**[[5ht6]] - Mll5 residues 323-458<br />
**[[5ht6]] - Mll5 residues 323-458<br />
**[[2kyu]] - hKHMT Mll Phd3 finger – NMR<br />
**[[2kyu]] - hKHMT Mll Phd3 finger – NMR<br />
**[[4gnd]] - hKHMT Nsd3 Phd5-C5HCH<br />
**[[6g3t]], [[6g3p]] - hKHMT Nsd3 residues 247-398<br />
**[[4gnd]] - hKHMT Nsd3 Phd5-C5HCH 1310-1413<br />
**[[4rxj]] - hKHMT Nsd3 residues 953-1064<br />
**[[4rxj]] - hKHMT Nsd3 residues 953-1064<br />
**[[5upd]]- hKHMT Nsd3 residues 1054-1285<br />
**[[5upd]]- hKHMT Nsd3 residues 1054-1285<br />
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**[[6by9]] - hKHMT EHMT1 residues 672-999<br />
**[[6by9]] - hKHMT EHMT1 residues 672-999<br />
**[[5v2n]] - hKHMT KMT5A residues 231-393<br />
**[[5v2n]] - hKHMT KMT5A residues 231-393<br />
**[[2j8a]] – KHMT SET1 RRM domain – yeast<br />
**[[1u2z]] – yKHMT C terminal<br />
**[[1ml9]] – NcKHMT Dim-5 – ''Neurospora crassa''<br />
**[[1ml9]] – NcKHMT Dim-5 – ''Neurospora crassa''<br />
**[[1n3j]] – PvKHMT – Paramecium bursaria chlorella virus<br />
**[[1n3j]] – PvKHMT – Paramecium bursaria chlorella virus<br />
**[[1u2z]] – yKHMT C terminal<br />
**[[2l7p]] – AtKHMT Ashh2 CW domain – ''Arabidopsis thaliana'' - NMR<br />
**[[2l7p]] – AtKHMT Ashh2 CW domain – ''Arabidopsis thaliana'' - NMR<br />
**[[2lxe]] – AtKHMT Suvr4 SET31 - NMR<br />
**[[2lxe]] – AtKHMT Suvr4 SET31 - NMR<br />
Line 107: Line 111:
**[[4wuy]], [[6cby]], [[6cbx]], [[5wcg]] - hKHMT Smyd2 + inhibitor<br />
**[[4wuy]], [[6cby]], [[6cbx]], [[5wcg]] - hKHMT Smyd2 + inhibitor<br />
**[[5cpr]] - hKHMT Suv420 SET domain + inhibitor<br />
**[[5cpr]] - hKHMT Suv420 SET domain + inhibitor<br />
**[[5w1y]] - hKHMT KMT5A SET domain (mutant) + inhibitor<br />
**[[6p0r]] - hKHMT Suv39h2 SET domain + inhibitor<br />
**[[5w1y]], [[6boz]] - hKHMT KMT5A SET domain (mutant) + inhibitor<br />
**[[5wbv]] - hKHMT KMT5B SET domain + inhibitor<br />
**[[5wbv]] - hKHMT KMT5B SET domain + inhibitor<br />
**[[5vsf]], [[5vsd]], [[5vpj]] - hKHMT EHMT1 SET domain + inhibitor<br />
**[[5vsf]], [[5vsd]], [[5vpj]] - hKHMT EHMT1 SET domain + inhibitor<br />
**[[5vse]], [[5vsc]], [[5vpi]] - hKHMT EHMT2 SET domain + inhibitor<br />
**[[5vse]], [[5vsc]], [[5vpi]] - hKHMT EHMT2 SET domain + inhibitor<br />
**[[6nm4]] - hKHMT Prdm9 zinc finger domain + inhibitor<br />
**[[6g2o]], [[6g2f]], [[6g2e]], [[6g2c]], [[6g2b]], [[6g29]], [[6g27]], [[6g25]], [[6g24]] - hKHMT Nsd3 residues 247-398 + inhibitor<br />


*Histone-lysine N-methyltransferase binary complexes with polypeptide
*Histone-lysine N-methyltransferase binary complexes with polypeptide
Line 118: Line 125:
**[[4gne]], [[4gnf]], [[4gng]] - hKHMT Nsd3 Phd5-C5HCH + H3 peptide<br />
**[[4gne]], [[4gnf]], [[4gng]] - hKHMT Nsd3 Phd5-C5HCH + H3 peptide<br />
**[[6cen]] - hKHMT Nsd3 + inhibitor peptide<br />
**[[6cen]] - hKHMT Nsd3 + inhibitor peptide<br />
**[[6mon]] - hKHMT Smyd2 + inhibitor peptide<br />
**[[3b95]] - hKHMT ankyrin repeat domain + H3 peptide<br />
**[[3b95]] - hKHMT ankyrin repeat domain + H3 peptide<br />
**[[6bhi]], [[6bhh]], [[6bhg]], [[6bhe]], [[6bhd]] - hKHMT SETDB1 tudor domain + H3 peptide<br />
**[[6bhi]], [[6bhh]], [[6bhg]], [[6bhe]], [[6bhd]] - hKHMT SETDB1 tudor domain + H3 peptide<br />
**[[3lqi]], [[3lqj]] - hKHMT Mll1 3rd Phd finger and bromodomain + H3 peptide<br />
**[[3lqi]], [[3lqj]] - hKHMT Mll1 3rd Phd finger and bromodomain + H3 peptide<br />
**[[6mlc]] - hKHMT Mll3 Phd7 domain + H4 peptide <br />
**[[6o7g]] - hKHMT Mll4 Phd6 domain + H4 peptide - NMR<br />
**[[5ex3]], [[5ex0]] - hKHMT Smyd3 + peptide<br />
**[[5ex3]], [[5ex0]] - hKHMT Smyd3 + peptide<br />
**[[5yvx]] - hKHMT Ashh2 CW domain + H3 peptide<br />
**[[5yvx]] - hKHMT Ashh2 CW domain + H3 peptide<br />
**[[6hbo]] - hKHMT Ashh2 CW domain + H3 peptide - NMR<br />
**[[4l58]] - hKHMT PHD-type zinc finger domain + H3 peptide<br />
**[[4l58]] - hKHMT PHD-type zinc finger domain + H3 peptide<br />
**[[6cko]] - zKHMT + AF-10 - zebrafish<br />
**[[6cko]] - zKHMT + AF-10 - zebrafish<br />
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**[[3vuz]], [[3vv0]] - hKHMT SET7/9 SET domain + deoxyadenosine derivative<br />
**[[3vuz]], [[3vv0]] - hKHMT SET7/9 SET domain + deoxyadenosine derivative<br />
**[[4x8p]], [[4x8n]] – hKHMT Ash2L Spry domain + RBBP5 <br />
**[[4x8p]], [[4x8n]] – hKHMT Ash2L Spry domain + RBBP5 <br />
**[[6e2h]] – hKHMT SET/Ash2 + DPY-30L <br />


*Histone-lysine N-methyltransferase ternary complex containing polypeptide
*Histone-lysine N-methyltransferase ternary complex containing polypeptide
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**[[1o9s]] - hKHMT SET7/9 SET domain + SAH + H3 peptide<br />
**[[1o9s]] - hKHMT SET7/9 SET domain + SAH + H3 peptide<br />
**[[2bqz]] - hKHMT SET7 SET domain + SAH + H4 peptide<br />
**[[2bqz]] - hKHMT SET7 SET domain + SAH + H4 peptide<br />
**[[6mbl]], [[6mbk]], [[6mbj]], [[6icv]], [[6ict]] - hKHMT SETD3 + SAH + actin peptide<br />
**[[3f9w]], [[3f9x]], [[3f9y]], [[3f9z]] - hKHMT SETD8 SET domain + SAH + H4 peptide<br />
**[[3f9w]], [[3f9x]], [[3f9y]], [[3f9z]] - hKHMT SETD8 SET domain + SAH + H4 peptide<br />
**[[5teg]] - hKHMT SETD8 SET domain + SAM + H4 peptide<br />
**[[5teg]] - hKHMT SETD8 SET domain + SAM + H4 peptide<br />
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**[[5v37]] – hKHMT Smyd3 + SAM + inhibitor<br />
**[[5v37]] – hKHMT Smyd3 + SAM + inhibitor<br />
**[[5hq8]] – hKHMT Smyd3 + SAH + MEKK2 peptide<br />
**[[5hq8]] – hKHMT Smyd3 + SAH + MEKK2 peptide<br />
**[[6ine]], [[6ago]] – hKHMT Ash1L + MRG15 + SAM <br />
**[[1zkk]] - hKHMT + SAH + H4 peptide <br />
**[[1zkk]] - hKHMT + SAH + H4 peptide <br />
**[[4c1q]] - hKHMT SET domain + SAH + H3 peptide <br />
**[[4c1q]] - hKHMT SET domain + SAH + H3 peptide <br />
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**[[4au7]] - mKHMT + SAH + H4 peptide - mouse<br />
**[[4au7]] - mKHMT + SAH + H4 peptide - mouse<br />


*Histone-lysine N-methyltransferase ternary complex containing inhibitor
*Histone-lysine N-methyltransferase ternary complex containing inhibitor; Domains – catalytic 879-1159; SET 1006-1266


**[[4e47]], [[4jds]], [[4jlg]], [[5ayf]] - hKHMT SET7/9 SET domain + SAM + inhibitor<br />
**[[4e47]], [[4jds]], [[4jlg]], [[5ayf]] - hKHMT SET7/9 SET domain + SAM + inhibitor<br />
**[[5ylt]] - hKHMT SET7/9 SET domain + sinefungin + inhibitor<br />
**[[5ylt]] - hKHMT SET7/9 SET domain + sinefungin + inhibitor<br />
**[[3fpd]], [[3k5k]], [[3mo0]], [[3mo2]], [[3mo5]], [[3rjw]], [[4nvq]] - hKHMT SET domain + SAH + inhibitor<br />
**[[3fpd]], [[3k5k]], [[3mo0]], [[3mo2]], [[3mo5]], [[3rjw]], [[4nvq]] - hKHMT SET domain + SAH + inhibitor<br />
**[[5tuz]] - hKHMT EHMT1 SET domain + SAH + inhibitor<br />
**[[5tuz]], [[6mbp]], [[6mbo]] - hKHMT EHMT1 SET domain + SAH + inhibitor<br />
**[[5ttg]] - hKHMT EHMT1 catalytic domain + SAM + inhibitor<br />
**[[5ttg]], [[5v9j]] - hKHMT EHMT1 catalytic domain + SAM + inhibitor<br />
**[[5tuy]] - hKHMT EHMT2 SET domain + SAM + inhibitor<br />
**[[5tuy]], [[5v9i]] - hKHMT EHMT2 SET domain + SAM + inhibitor<br />
**[[5ttf]] - hKHMT EHMT2 catalytic domain + SAM + inhibitor<br />
**[[5ttf]] - hKHMT EHMT2 catalytic domain + SAM + inhibitor<br />
**[[3s7b]], [[5kjn]], [[5kjm]], [[5kjl]], [[5kjk]], [[5arg]], [[5arf]], [[4ynd]] - hKHMT Smyd2 + SAM + inhibitor<br />
**[[3s7b]], [[5kjn]], [[5kjm]], [[5kjl]], [[5kjk]], [[5arg]], [[5arf]], [[4ynd]] - hKHMT Smyd2 + SAM + inhibitor<br />
**[[5ccm]], [[5ccl]] – hKHMT Smyd3 + SAM + inhibitor<br />
**[[5ccm]], [[5ccl]], [[5yjo]], [[5xxj]], [[5xxg]], [[5xxd]] – hKHMT Smyd3 + SAM + inhibitor<br />
**[[1zkk]] - hKHMT + SAH + H4 peptide <br />
**[[1zkk]] - hKHMT + SAH + H4 peptide <br />
**[[4qen]], [[4qeo]], [[4qep]] – AtKHMT Suvh4 + DNA + SAH<br />
**[[4qen]], [[4qeo]], [[4qep]] – AtKHMT Suvh4 + DNA + SAH<br />
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**[[5hq2]] - hKHMT SETD8 SET domain + H3 + H4 + H2 + SRM1 + DNA<br />
**[[5hq2]] - hKHMT SETD8 SET domain + H3 + H4 + H2 + SRM1 + DNA<br />
**[[6jm9]] - hKHMT DOT1 + H3.2 + H4 + H2A + H2B + DNA – Cryo EM<br />
**[[6o96]], [[6nqa]], [[6nog]], [[6nn6]], [[6nj9]], [[6jma]], [[6j99]] - hKHMT DOT1 + H3.2 + H4 + H2A + H2B + polyubiquitin + DNA – Cryo EM<br />
**[[5t0m]], [[5t0k]] - hKHMT EHMT2 SET domain + SAM + SAH + H3 peptide<br />
**[[5t0m]], [[5t0k]] - hKHMT EHMT2 SET domain + SAM + SAH + H3 peptide<br />
**[[5ls6]], [[5hyn]] - hKHMT Ezh2 + polycomb protein + Jarid2 + inhibitor<br />
**[[5ls6]], [[5hyn]] - hKHMT Ezh2 + polycomb protein + Jarid2 + inhibitor<br />
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*Histone-arginine N-methyltransferase (Carm1)
*Histone-arginine N-methyltransferase (Carm1)


**[[2v74]], [[2v7e]] – mRHMT catalytic domain <br />
**[[4qqk]] – hPRMT6 <br />
**[[4c03]], [[4c06]], [[4c07]], [[4c08]], [[5hzm]] – mRHMT  6<br />
**[[4hc4]] – hPRMT6 (mutant)<br />
**[[2obq]] – rRHMT N terminal - rat <br />
**[[2v74]], [[2v7e]] – mPRMT catalytic domain <br />
**[[3b3g]], [[3b3j]] – rRHMT catalytic domain <br />
**[[4c03]], [[4c06]], [[4c07]], [[4c08]], [[5hzm]] – mPRMT6<br />
**[[4qqk]] – hRHMT 6 <br />
**[[2obq]] – rPRMT N terminal - rat <br />
**[[4hc4]] – hRHMT 6 (mutant)<br />
**[[3b3g]], [[3b3j]] – rPRMT catalytic domain <br />


*Histone-arginine N-methyltransferase (Carm1) binary complex
*Histone-arginine N-methyltransferase (Carm1) binary complex


**[[5ih3]] – mRHMT  4 + SAH<br />
**[[5u4x]] – hPRMT1 catalytic domain + SAH<br />
**[[5k8v]], [[5isi]], [[5ish]], [[5isg]], [[5isf]], [[5ise]], [[5isd]], [[5isc]], [[5isb]], [[5isa]], [[5is9]], [[5is8]], [[5is7]], [[5is6]], [[5tbj]], [[5tbi]], [[5tbh]], [[5ntc]], [[5lkj]], [[5k8x]], [[5k8w]] – mRHMT  4 + inhibitor<br />
**[[6nt2]] – hPRMT1 residues 1-371 + inhibitor<br />
**[[5lgs]], [[5lgr]], [[5lgq]], [[5lgp]] – mRHMT  4 + poly(A)-binding protein peptide + inhibitor<br />
**[[5dxj]] – hPRMT4 catalytic domain + sinefungin <br />
**[[4c04]] – mRHMT  6 + inhibitor<br />
**[[4ikp]], [[6d2l]], [[6dvr]] – hPRMT4 catalytic domain + purine derivative<br />
**[[4c05]], [[5fqo]], [[5fqn]] – mRHMT  6 + SAH<br />
**[[5egs]], [[5wcf]], [[5lv5]], [[5lv4]], [[5lv3]], [[5lv2]] – hPRMT6 + inhibitor<br />
**[[4c4a]] – mRHMT  7 + SAH<br />
**[[5ih3]] – mPRMT4 + SAH<br />
**[[3b3f]] – rRHMT catalytic domain + SAH<br />
**[[5k8v]], [[5isi]], [[5ish]], [[5isg]], [[5isf]], [[5ise]], [[5isd]], [[5isc]], [[5isb]], [[5isa]], [[5is9]], [[5is8]], [[5is7]], [[5is6]], [[5tbj]], [[5tbi]], [[5tbh]], [[5ntc]], [[5lkj]], [[5k8x]], [[5k8w]] – mPRMT4 + inhibitor<br />
**[[5u4x]] – hRHMT 1 catalytic domain + SAH<br />
**[[5lgs]], [[5lgr]], [[5lgq]], [[5lgp]] – mPRMT4 + poly(A)-binding protein peptide + inhibitor<br />
**[[5dxj]] – hRHMT 4 catalytic domain + sinefungin <br />
**[[4c04]] – mPRMT6 + inhibitor<br />
**[[4ikp]], [[6d2l]] – hRHMT 4 catalytic domain + purine derivative<br />
**[[4c05]], [[5fqo]], [[5fqn]] – mPRMT6 + SAH<br />
**[[5egs]], [[5wcf]], [[5lv5]], [[5lv4]], [[5lv3]], [[5lv2]] – hRHMT 6 + inhibitor<br />
**[[4c4a]] – mPRMT7 + SAH<br />
**[[6ogn]] – mPRMT7 + inhibitor<br />
**[[3b3f]] – rPRMT catalytic domain + SAH<br />


*Histone-arginine N-methyltransferase (Carm1) ternary complex
*Histone-arginine N-methyltransferase (Carm1) ternary complex


**[[5lgs]], [[5lgr]], [[5lgq]], [[5lgp]] – mRHMT  4 + poly(A)-binding protein peptide + inhibitor<br />
**[[5dxa]], [[5dx8]], [[5dx1]] – hPRMT4 catalytic domain + sinefungin + peptide<br />
**[[5dxa]], [[5dx8]], [[5dx1]] – hRHMT 4 catalytic domain + sinefungin + peptide<br />
**[[5dx0]], [[5dwq]] – hPRMT4 catalytic domain + sinefungin + H3 peptide<br />
**[[5dx0]], [[5dwq]] – hRHMT 4 catalytic domain + sinefungin + H3 peptide<br />
**[[2y1w]], [[2y1x]] – hPRMT4 catalytic domain + sinefungin + indole inhibitor<br />
**[[2y1w]], [[2y1x]] – hRHMT 4 catalytic domain + sinefungin + indole inhibitor<br />
**[[6arv]], [[6arj]] – hPRMT4 catalytic domain + SAH + inhibitor<br />
**[[6arv]], [[6arj]] – hRHMT 4 catalytic domain + SAH + inhibitor<br />
**[[5lgs]], [[5lgr]], [[5lgq]], [[5lgp]] – mPRMT 4 + poly(A)-binding protein peptide + inhibitor<br />
**[[4gqb]], [[5fa5]] – hRHMT 5 + methylosome protein 50 + H4 peptide<br />
**[[4gqb]], [[5fa5]] – hPRMT5 + methylosome protein 50 + H4 peptide<br />
**[[5emm]] – hRHMT 5 + methylosome protein 50 + sinefungin<br />
**[[5emm]] – hPRMT5 + methylosome protein 50 + sinefungin<br />
**[[5eml]] – hRHMT 5 + methylosome protein 50 + SAM<br />
**[[6k1s]] – hPRMT5 + methylosome protein 50 + inhibitor<br />
**[[5emk]], [[5emj]], [[5c9z]] – hRHMT 5 + methylosome protein 50 + sinefungin + inhibitor<br />
**[[5eml]] – hPRMT5 + methylosome protein 50 + SAM<br />
**[[4x63]], [[4x61]], [[4x60]] – hRHMT 5 + methylosome protein 50 + SAH + inhibitor<br />
**[[5emk]], [[5emj]], [[5c9z]] – hPRMT5 + methylosome protein 50 + sinefungin + inhibitor<br />
**[[6ckc]] – hRHMT 5 + methylsome protein 50 + inhibitor<br />
**[[4x63]], [[4x61]], [[4x60]] – hPRMT5 + methylosome protein 50 + SAH + inhibitor<br />
**[[5e8r]], [[4y30]], [[4y2h]] – hRHMT 6 + SAH + inhibitor<br />
**[[6ckc]] – hPRMT5 + methylosome protein 50 + inhibitor<br />
**[[4qpp]] – hRHMT 6 (mutant) + peptide + inhibitor<br />
**[[5e8r]], [[4y30]], [[4y2h]], [[6p7i]] – hPRMT6 + SAH + inhibitor<br />
**[[4qpp]] – hPRMT6 (mutant) + peptide + inhibitor<br />
 


}}
}}

Revision as of 10:44, 1 August 2019


Function

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[1]. 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.

Relevance

Inhibitors of the histone-lysine N-methyltransferase SMYD2 which represses the tumor-suppressing activities of p53 are studied as cancer therapy drugs[2].

Disease

Aberrant HMT plays a role in cancer, intellectual disability syndromes and regulation of tissue aging[3].

Structural highlights

Human inserted in a hydrophobic environment[4]. Water molecules shown as red spheres

3D Structures of histone methyltransferase

Histone methyltransferase 3D structures


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

3D Structures of histone methyltransferase3D Structures of histone methyltransferase

Updated on 01-August-2019

ReferencesReferences

  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

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

Michal Harel, Alexander Berchansky, Joel L. Sussman
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