Download MendeleyA Water-Bridged H-Bonding Network Contributes to the Catalysis of the SAM-Dependent C-Methyltransferase HcgC.
Bai, L., Wagner, T., Xu, T., Hu, X., Ermler, U., Shima, S.(2017) Angew Chem Int Ed Engl 56: 10806-10809
- PubMed: 28682478
- DOI: https://doi.org/10.1002/anie.201705605
- Primary Citation of Related Structures:
5O4H, 5O4J, 5O4M, 5O4N - PubMed Abstract:
[Fe]-hydrogenase hosts an iron-guanylylpyridinol (FeGP) cofactor. The FeGP cofactor contains a pyridinol ring substituted with GMP, two methyl groups, and an acylmethyl group. HcgC, an enzyme involved in FeGP biosynthesis, catalyzes methyl transfer from S-adenosylmethionine (SAM) to C3 of 6-carboxymethyl-5-methyl-4-hydroxy-2-pyridinol (2). We report on the ternary structure of HcgC/S-adenosylhomocysteine (SAH, the demethylated product of SAM) and 2 at 1.7 Å resolution. The proximity of C3 of substrate 2 and the S atom of SAH indicates a catalytically productive geometry. The hydroxy and carboxy groups of substrate 2 are hydrogen-bonded with I115 and T179, as well as through a series of water molecules linked with polar and a few protonatable groups. These interactions stabilize the deprotonated state of the hydroxy groups and a keto form of substrate 2, through which the nucleophilicity of C3 is increased by resonance effects. Complemented by mutational analysis, a structure-based catalytic mechanism was proposed.
Organizational Affiliation:
Max-Planck-Institut für terrestrische Mikrobiologie, Karl-von-Frisch-Straße 10, 35043, Marburg, Germany.
