title: Structure, function and physiological role of glycine N-methyltransferase.
abstract: Glycine N-methyltransferase (EC 2.1.1.20) catalyzes the transfer of the methyl group of S-adenosylmethionine (AdoMet) to glycine to form S-adenosylhomocysteine and sarcosine. Unlike most AdoMet-dependent methyltransferases, glycine N-methyltransferase is a tetramer of identical subunits. Crystallography of recombinant rat glycine N-methyltransferase indicates that four nearly spherical subunits are arranged to form a flat, square tetramer with a large hole in the centre. The enzyme occurs abundantly in the livers of rat, rabbit and mouse. Glycine N-methyltransferases from rat, rabbit, human and pig livers are shown to have similar amino acid sequences and, with the enzymes from rat and rabbit livers, it is demonstrated that the N-terminal valine is acetylated. Glycine N-methyltransferases from livers exhibit sigmoidal rate behaviour with respect to AdoMet and hyperbolic behaviour with respect to glycine at all pH tested. However, recombinant rat glycine N-methyltransferase which lacks the N-terminal acetyl group shows no cooperativity toward AdoMet at neutral pH, suggesting that elimination of the positive charge at the N-terminus is required for cooperative behaviour. Glycine N-methyltransferase binds 5-methyltetrahydropteroylpentaglutamate tightly, resulting in inhibition of the catalytic activity. The nature of these unique functional features is discussed in the light of the three-dimensional structure of the enzyme. The tissue and subcellular localization of the enzyme and its possible role in methionine metabolism are reviewed.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ogawa
authors.forename: T
authors.initials: T
authors.lastname: Gomi
authors.forename: F
authors.initials: F
authors.lastname: Takusagawa
authors.forename: M
authors.initials: M
authors.lastname: Fujioka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002384:Catalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005998:Glycine / Q000737:chemistry / Q000378:metabolism; D050938:Glycine N-Methyltransferase; D006801:Humans; D008099:Liver / Q000201:enzymology; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D011624:Pteroylpolyglutamic Acids / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; D011624:Pteroylpolyglutamic Acids; C044774:5-methyltetrahydropteroylpentaglutamate; D012436:S-Adenosylmethionine; D008780:Methyltransferases; D050938:Glycine N-Methyltransferase; D005998:Glycine