Histone methyltransferase: Difference between revisions

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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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]] }}
+<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'>
-'''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.
+== 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<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.
-{{TOC limit|limit=2}}
+For SET7/9 see [[Histone Lysine Methyltransferase SET7/9]].
-== 3D Structures of histone methyltransferase ==
+*'''euchromatin histone methyltransferase''' dimethylates histone H3 at Lys 9 resulting in transcriptional repression<ref>PMID:32684241</ref>.
+*'''DOT1L histone methyltransferase''' methylates histone H3 at Lys 79 resulting in transcriptional repression<ref>PMID:35495127</ref>.
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+== Relevance ==
+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>.
-[[1nw3]] – hHMT DOT1L – human
+== Disease ==
+Aberrant HMT plays a role in cancer, intellectual disability syndromes and regulation of tissue aging<ref>PMID:22473383</ref>.
-[[2igq]] – hHMT-1 C terminal
+== 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
-===Histone-lysine N-methyltransferase===
+== 3D Structures of histone methyltransferase ==
+[[Histone methyltransferase 3D structures]]
-[[2j8a]] – KHMT SET1 RRM domain – yeast
-[[3s8s]] – hKHMT SETD1A RRM domain<br />
-[[2r3a]] – hKHMT Suv39H2<br />
-[[3rq4]] - hKHMT Suv420H2<br />
-[[3s8p]] - hKHMT Suv420H1<br />
-[[3mts]] - hKHMT Suv39H1 chromo domain<br />
-[[1h3i]] - hKHMT Set7/9 residues 52-344<br />
-[[2o8j]] - hKHMT H3K9 residues 913-1193<br />
-[[2lv9]] - hKHMT Mll5 residues 109-188 - NMR<br />
-[[3n71]] - hKHMT Smyd1<br />
-[[1ml9]] – NcKHMT Dim-5 – ''Neurospora crassa''<br />
-[[1n3j]] – PvKHMT – Paramecium bursaria chlorella virus<br />
-[[1u2z]] – yKHMT C terminal
-===Histone-lysine N-methyltransferase complexes===
-[[3rib]] – hKHMT Smyd2 + SAH<br />
-[[1o9s]] - hKHMT Set7/9 Set domain + SAH + H3 peptide<br />
-[[2bqz]] - hKHMT Set7 Set domain + SAH + H4 peptide<br />
-[[1mt6]] - hKHMT Set7/9 residues 58-337 + SAH<br />
-[[1n6a]] – hKHMT SET7/9 SET domain + SAM<br />
-[[1n6c]] – hKHMT SET7/9 residues 70-366 + SAM<br />
-[[1xqh]] - hKHMT SET7/9 SET domain + SAH + p53 peptide<br />
-[[2f69]], [[3m53]] - hKHMT SET7/9 SZET domain + SAH + TAF10 peptide<br />
-[[3m54]], [[3m55]], [[3m56]], [[3m57]], [[3m58]], [[3m59]], [[3m5a]] - hKHMT SET7/9 SET domain (mutant) + SAH + TAF10 peptide<br />
-[[3cbm]] - hKHMT SET7/9 SET domain + SAM + estrogen receptor peptide<br />
-[[4e47]], [[4jds]], [[4jlg]] - hKHMT SET7/9 SET domain + SAM + inhibitor<br />
-[[3cbo]] - hKHMT SET7/9 SET domain + SAH + estrogen receptor peptide<br />
-[[3os5]] - hKHMT SET7/9 SET domain + SAH + DNMT1 peptide<br />
-[[3cbp]] - hKHMT SET7/9 SET domain + sinefungin<br />
-[[3vuz]], [[3vv0]] - hKHMT SET7/9 SET domain + deoxyadenosine derivative<br />
-[[3s7b]] - hKHMT Smyd2 + SAM + inhibitor
-[[3s7d]], [[3s7f]], [[3tg5]] - hKHMT Smyd2 + SAH + p53 peptide
-[[3s7j]], [[3tg4]] - hKHMT Smyd2 + SAM<br />
-[[1peg]] - NcKHMT Dim-5 + SAH + H3 peptide<br />
-[[2g46]] – PvKHMT + SAH + H3 peptide<br />
+</StructureSection>
+== References ==
+<references/>
 [[Category:Topic Page]]