Abstract
Protein lysine methylation by SET domain enzymes regulates chromatin structure, gene silencing, transcriptional activation, plant metabolism, and other processes. The 2.6 A resolution structure of Rubisco large subunit methyltransferase in a pseudo-bisubstrate complex with S-adenosylhomocysteine and a HEPES ion reveals an all-beta architecture for the SET domain embedded within a larger alpha-helical enzyme fold. Conserved regions of the SET domain bind S-adenosylmethionine and substrate lysine at two sites connected by a pore. We propose that methyl transfer is catalyzed by a conserved Tyr at a narrow pore connecting the sites. The cofactor enters by a "back door" on the opposite side of the enzyme from substrate, promoting highly specific protein recognition and allowing addition of multiple methyl groups.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Binding Sites
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Chromatin / chemistry
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Conserved Sequence
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DNA Mutational Analysis
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DNA-Binding Proteins / chemistry*
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Dimerization
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Dose-Response Relationship, Drug
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Drosophila Proteins / chemistry*
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Electrons
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Gene Silencing
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HEPES / pharmacology
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Histones / chemistry
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Kinetics
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Ligands
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Lysine / chemistry
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Models, Chemical
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Models, Molecular
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Molecular Sequence Data
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Nuclear Proteins / chemistry*
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Pisum sativum / enzymology
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Polycomb Repressive Complex 2
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Protein Binding
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Protein Methyltransferases / chemistry*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Repressor Proteins / chemistry*
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Spinacia oleracea / enzymology
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Substrate Specificity
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Transcription Factors*
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Transcriptional Activation
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Tyrosine / chemistry
Substances
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Chromatin
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DNA-Binding Proteins
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Drosophila Proteins
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Histones
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Ligands
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Nuclear Proteins
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Repressor Proteins
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Transcription Factors
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Trl protein, Drosophila
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Tyrosine
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Protein Methyltransferases
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E(z) protein, Drosophila
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Polycomb Repressive Complex 2
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Lysine
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HEPES