The active site of the SET domain is constructed on a knot.
The SET domain contains the catalytic center of lysine methyltransferases that target the N-terminal tails of histones and regulate chromatin function. Here we report the structure of the SET7/9 protein in the absence and presence of its cofactor product, S-adenosyl-L-homocysteine (AdoHcy). A knot within the SET domain helps form the methyltransferase active site, where AdoHcy binds and lysine methylation is likely to occur. A structure-guided comparison of sequences within the SET protein family suggests that the knot substructure and active site environment are conserved features of the SET domain.
Jacobs
Steven A
SA
Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Harp
Joel M
JM
Devarakonda
Srikripa
S
Kim
Youngchang
Y
Rastinejad
Fraydoon
F
Khorasanizadeh
Sepideh
S
D000595:Amino Acid Sequence; D001665:Binding Sites; D003067:Coenzymes / Q000737:chemistry; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008780:Methyltransferases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011496:Protein Methyltransferases; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012435:S-Adenosylhomocysteine / Q000737:chemistry; D016415:Sequence Alignment
D003067:Coenzymes; D011994:Recombinant Proteins; D012435:S-Adenosylhomocysteine; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human