title: Crystal structure of apo-glycine N-methyltransferase (GNMT).
abstract: The crystal structure of the recombinant apo-form of glycine N-methyltransferase (GNMT) has been determined at 2.5 A resolution. GNMT is a tetrameric enzyme (monomer Mr = 32,423Da, 292 amino acids) that catalyzes the transfer of a methyl group from S-adenosylmethionine (AdoMet) to glycine with the formation of S-adenosylhomocysteine (AdoHcy) and sarcosine (N-methylglycine). GNMT is a regulatory enzyme, which is inhibited by 5-methyltetrahydrofolate pentaglutamate and believed to control the ratio of AdoMet to AdoHcy in tissues. The crystals belong to the orthorhombic space group P2(1)2(1)2 (a = 85.39, b = 174.21, c = 44.71 A) and contain one dimer per asymmetric unit. The AdoMet-GNMT structure served as the starting model. The structure was refined to an R-factor of 21.9%. Each monomer is a three-domain structure with a large cavity enclosed by the three domains. The tetramer resembles a square with a central channel about which N-terminal domains are intertwined. Only localized changes of the residues involved in the binding pocket are observed for the apo-GNMT structure when compared to that determined in the presence of substrate and substrate analog.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. pattanr@ctrvax.Vanderbilt.edu
authors.forename: R
authors.initials: R
authors.lastname: Pattanayek
authors.forename: M E
authors.initials: ME
authors.lastname: Newcomer
authors.forename: C
authors.initials: C
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001051:Apoenzymes / Q000737:chemistry*; D003460:Crystallization; D019281:Dimerization; D050938:Glycine N-Methyltransferase; D008099:Liver / Q000201:enzymology; D046911:Macromolecular Substances; D008780:Methyltransferases / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D001051:Apoenzymes; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D008780:Methyltransferases; D050938:Glycine N-Methyltransferase; C494512:Gnmt protein, rat