Document Type

Article

Publication Date

1-1-1998

Abstract

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 M(r) = 32,423D(a), 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 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.

Publication Source (Journal or Book title)

Protein Science

First Page

1326

Last Page

1331

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