5O4N

Apo HcgC from Methanococcus maripaludis soaked with SAH and pyridinol

Summary for 5O4N

• Entry DOI: 10.2210/pdb5o4n/pdb
• Descriptor: HcgC, S-ADENOSYL-L-HOMOCYSTEINE, 6-carboxy methyl-4-hydroxy-2-pyridinol, ... (6 entities in total)
• Functional Keywords: methyltransferases, biosynthesis, protein structures, enzyme catalysis, mutagenesis, [fe]-hydrogenase, pyridinol, hmd, transferase
• Biological source: Methanococcus maripaludis S2
• Total number of polymer chains: 4
• Total formula weight: 126944.18

Authors

Wagner, T.,Bai, L.,Xu, T.,Hu, X.,Ermler, U.,Shima, S. (deposition date: 2017-05-29, release date: 2017-07-19, Last modification date: 2024-01-17)

Primary citation

Bai, L.,Wagner, T.,Xu, T.,Hu, X.,Ermler, U.,Shima, S.
A Water-Bridged H-Bonding Network Contributes to the Catalysis of the SAM-Dependent C-Methyltransferase HcgC.
Angew. Chem. Int. Ed. Engl., 56:10806-10809, 2017

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.

PubMed: 28682478
DOI: 10.1002/anie.201705605

Experimental method

X-RAY DIFFRACTION (2.05 Å)