Crystal structure of apo‐glycine N‐methyltransferase (GNMT)

The crystal structure of the recombinant apo‐form of glycine N‐methyltransferase (GNMT) has been determined at 2.5 Å 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‐adenosylmethionine (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 P21212 (a = 85.39, b = 174.21, c = 44.71 Å) 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.