STRUCTURE AND FUNCTION OF GLYCINE METHYLTRANSFERASE FROM RAT LIVER. Zhuji Fu, Yongbo Hu, Fusao Takusagawa, Departments of Chemistry and Biochemistry, University of Kansas, Lawrence, KS 66045-0045, Kiyoshi Konishi, Yoshimi Takata and Motoji Fujioka, Department of Biochemistry, Toyama Medical and Pharmaccutical University, Faculty of Medicine, Sugitani, Toyama 930-01, Japan

Biological methylation reactions utilizing S-adenosylmethionine (AdoMet) as the methyl donor are widespread in nature, and participate in a wide variety of cellular processes through methylation of nucleic acids, proteins, phospholipids, and small molecules. Glycine methyltransferase (S-adenosyl-L-methionine:glycine methyltransferase, EC 2.1.1.20; GMT) catalyzes the AdoMet-dependent methylation of glycine to form sarcosine. GMT, unlike most AdoMet-dependent methyltransferases, is an oligomeric protein consisting of four identical subunits. The enzyme was crystallized by the hanging drop vapor diffusion method. The crystal belongs to the orthorhombic space group P2₁2_l2, with unit cel1 dimensions of a= 86.4, b= 175.7, c= 45.5 Å and with two subunits in the asymmetric unit. The crystal structure has been determined at 2.4 Å resolution by MIR method. The current crystallographic R-factor is 0.19 for all data. In the structure, the N-terminal regions (l-20 residues) are far from the subunit and go into the opposite subunit. Furthermore, Glu15 is involved in formation of the active site of the opposite subunit. The detailed active site geometry and the AdoMet binding scheme will be described along with the catalytic mechanism of GMT at the meeting.