Download MendeleyCrystal structure of the s-adenosylmethionine synthetase ternary complex: a novel catalytic mechanism of s-adenosylmethionine synthesis from ATP and MET.
Komoto, J., Yamada, T., Takata, Y., Markham, G.D., Takusagawa, F.(2004) Biochemistry 43: 1821-1831
- PubMed: 14967023
- DOI: https://doi.org/10.1021/bi035611t
- Primary Citation of Related Structures:
1P7L, 1RG9 - PubMed Abstract:
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 coli MAT (eMAT) has been crystallized with the ATP analogue AMPPNP and Met, and the crystal structure has been determined at 2.5 A resolution. eMAT is a dimer of dimers and has a 222 symmetry. Each active site contains the products SAM and PPNP. A modeling study indicates that the substrates (AMPPNP and Met) can bind at the same sites as the products, and only a small conformation change of the ribose ring is needed for conversion of the substrates to the products. On the basis of the ternary complex structure and 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 the ribose ring conformation from C4'-exo to C3'-endo occurs, and the S of Met makes a nucleophilic attack on the C5' to form SAM. All essential amino acid residues for substrate binding found in eMAT are conserved in the rat liver enzyme, indicating that the bacterial and mammalian enzymes have the same catalytic mechanism. However, a catalytic mechanism proposed recently by Gonz¨¢lez et al. based on the structures of three ternary complexes of rat liver MAT [Gonz¨¢lez, B., Pajares, M. A., Hermoso, J. A., Guillerm, D., Guillerm, G., and Sanz-Aparicio. J. (2003) J. Mol. Biol. 331, 407] is substantially different from our mechanism.
Organizational Affiliation:
Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045-7534, USA.
