1rg9
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S-Adenosylmethionine synthetase complexed with SAM and PPNP
OverviewOverview
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 Gonzalez et al. based, on the structures of three ternary complexes of rat liver MAT [Gonzalez, 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.
About this StructureAbout this Structure
1RG9 is a Single protein structure of sequence from Escherichia coli with K, MG, SAM and PPK as ligands. Active as Methionine adenosyltransferase, with EC number 2.5.1.6 Full crystallographic information is available from OCA.
ReferenceReference
Crystal 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 GD, Takusagawa F, Biochemistry. 2004 Feb 24;43(7):1821-31. PMID:14967023
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