1NBH

Structure of glycine N-methyltransferase complexed with S-adenosylmethionine and acetate, GNMT:SAM:Ace

Summary for 1NBH

• Entry DOI: 10.2210/pdb1nbh/pdb
• Related: 1NBI
• Descriptor: Glycine N-methyltransferase, ACETATE ION, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: methyltransferase, glycine n-methyltransferase, s-adenosylmethionine, enzyme catalytic mechanism, transferase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm: P13255
• Total number of polymer chains: 4
• Total formula weight: 131673.24

Authors

Takata, Y.,Takusagawa, F. (deposition date: 2002-12-02, release date: 2003-03-04, Last modification date: 2024-02-14)

Primary citation

Takata, Y.,Huang, Y.,Komoto, J.,Yamada, T.,Konishi, K.,Ogawa, H.,Gomi, T.,Fujioka, M.,Takusagawa, F.
Catalytic mechanism of glycine N-methyltransferase
Biochemistry, 42:8394-8402, 2003

PubMed Abstract: Methyltransfer reactions are some of the most important reactions in biological systems. Glycine N-methyltransferase (GNMT) catalyzes the S-adenosyl-l-methionine- (SAM-) dependent methylation of glycine to form sarcosine. Unlike most SAM-dependent methyltransferases, GNMT has a relatively high value and is weakly inhibited by the product S-adenosyl-l-homocysteine (SAH). The major role of GNMT is believed to be the regulation of the cellular SAM/SAH ratio, which is thought to play a key role in SAM-dependent methyltransfer reactions. Crystal structures of GNMT complexed with SAM and acetate (a potent competitive inhibitor of Gly) and the R175K mutated enzyme complexed with SAM were determined at 2.8 and 3.0 A resolutions, respectively. With these crystal structures and the previously determined structures of substrate-free enzyme, a catalytic mechanism has been proposed. Structural changes occur in the transitions from the substrate-free to the binary complex and from the binary to the ternary complex. In the ternary complex stage, an alpha-helix in the N-terminus undergoes a major conformational change. As a result, the bound SAM is firmly connected to protein and a "Gly pocket" is created near the bound SAM. The second substrate Gly binds to Arg175 and is brought into the Gly pocket. Five hydrogen bonds connect the Gly in the proximity of the bound SAM and orient the lone pair orbital on the amino nitrogen (N) of Gly toward the donor methyl group (C(E)) of SAM. Thermal motion of the enzyme leads to a collision of the N and C(E) so that a S(N)2 methyltransfer reaction occurs. The proposed mechanism is supported by mutagenesis studies.

PubMed: 12859184
DOI: 10.1021/bi034245a

Experimental method

X-RAY DIFFRACTION (2.8 Å)