Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT
Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT
- Nature Structural Biology, 10(7), p.545-552, 2003 .
SET domain protein methyltransferases catalyze the transfer of methyl groups from the cofactor S-adenosylmethionine (AdoMet)to specific lysine residues of protein substrates, such as the N-terminal tails of histones H3 and H4 and the large subunit of the Rubisco holoenzyme complex. The crystal structures of pea Rubisco large subunit methyltransferase (LSMT)in ternary complexes with either lysine or e-N-methyllysine (MeLys)and the product S-adenosylhomocysteine (AdoHcy)were determined to resolutions of 2.65 and 2.55 Å, respectively. The ?-methyl group of MeLys is bound to the enzyme via carbon-oxygen hydrogen bonds that play a key role in catalysis. The methyl donor and acceptor are aligned in a linear geometry for SN2 nucleophilic transfer of the methyl group during catalysis. Differences in hydrogen bonding between the MeLys e-amino group and Rubisco LSMT and SET7/9 explain why Rubisco LSMT generates multiply methylated Lys, wheras SET7/9 generates only MeLys.
EPSILON N METHYLLYSINE
HISTONE H3
HISTONE H4
HOLOENZYME
LARGE SUBUNIT METHYLTRANSFERASE
LYSINE
LYSINE DERIVATIVE
METHYL GROUP
PROTEIN
PROTEIN METHYLTRANSFERASE
RIBULOSEBISPHOSPHATE CARBOXYLASE
S ADENOSYLHOMOCYSTEINE
S ADENOSYLMETHIONINE
SET DOMAIN PROTEIN
UNCLASSIFIED DRUG
SET domain protein methyltransferases catalyze the transfer of methyl groups from the cofactor S-adenosylmethionine (AdoMet)to specific lysine residues of protein substrates, such as the N-terminal tails of histones H3 and H4 and the large subunit of the Rubisco holoenzyme complex. The crystal structures of pea Rubisco large subunit methyltransferase (LSMT)in ternary complexes with either lysine or e-N-methyllysine (MeLys)and the product S-adenosylhomocysteine (AdoHcy)were determined to resolutions of 2.65 and 2.55 Å, respectively. The ?-methyl group of MeLys is bound to the enzyme via carbon-oxygen hydrogen bonds that play a key role in catalysis. The methyl donor and acceptor are aligned in a linear geometry for SN2 nucleophilic transfer of the methyl group during catalysis. Differences in hydrogen bonding between the MeLys e-amino group and Rubisco LSMT and SET7/9 explain why Rubisco LSMT generates multiply methylated Lys, wheras SET7/9 generates only MeLys.
EPSILON N METHYLLYSINE
HISTONE H3
HISTONE H4
HOLOENZYME
LARGE SUBUNIT METHYLTRANSFERASE
LYSINE
LYSINE DERIVATIVE
METHYL GROUP
PROTEIN
PROTEIN METHYLTRANSFERASE
RIBULOSEBISPHOSPHATE CARBOXYLASE
S ADENOSYLHOMOCYSTEINE
S ADENOSYLMETHIONINE
SET DOMAIN PROTEIN
UNCLASSIFIED DRUG