Crystal Structure of the S-Adenosylmethionine Synthetase Ternary Complex: A Novel Catalytic Mechanism of S-Adenosylmethionine Synthesis from ATP and Met

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• 作者：Junichi Komoto ; Taro Yamada ; Yoshimi Takata ; George D. Markham ; and Fusao Takusagawa
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：February 24, 2004
• 年：2004
• 卷：43
• 期：7
• 页码：1821 - 1831
• 全文大小：568K
• 年卷期：v.43,no.7(February 24, 2004)
• ISSN：1520-4995

文摘

S-Adenosylmethionine synthetase (MAT) catalyzes formation of S-adenosylmethionine (SAM)from ATP and L-methionine (Met) and hydrolysis of tripolyphosphate to PP_i and P_i. Escherichia coliMAT (eMAT) has been crystallized with the ATP analogue AMPPNP and Met, and the crystal structurehas been determined at 2.5 Å resolution. eMAT is a dimer of dimers and has a 222 symmetry. Eachactive site contains the products SAM and PPNP. A modeling study indicates that the substrates (AMPPNPand Met) can bind at the same sites as the products, and only a small conformation change of the ribosering is needed for conversion of the substrates to the products. On the basis of the ternary complex structureand a modeling study, a novel catalytic mechanism of SAM formation is proposed. In the mechanism,neutral His14 acts as an acid to cleave the C5'-O5' bond of ATP while simultaneously a change in theribose ring conformation from C4'-exo to C3'-endo occurs, and the S of Met makes a nucleophilic attackon the C5' to form SAM. All essential amino acid residues for substrate binding found in eMAT areconserved in the rat liver enzyme, indicating that the bacterial and mammalian enzymes have the samecatalytic mechanism. However, a catalytic mechanism proposed recently by González et al. based on thestructures of three ternary complexes of rat liver MAT [González, B., Pajares, M. A., Hermoso, J. A.,Guillerm, D., Guillerm, G., and Sanz-Aparicio. J. (2003) J. Mol. Biol. 331, 407] is substantially differentfrom our mechanism.