5O4H

HcgC from Methanococcus maripaludis cocrystallized with SAM and pyridinol

5O4H の概要

• エントリーDOI: 10.2210/pdb5o4h/pdb
• 分子名称: HcgC, S-ADENOSYL-L-HOMOCYSTEINE, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: methyltransferases, biosynthesis, protein structures, enzyme catalysis, mutagenesis, [fe]-hydrogenase, pyridinol, hmd, transferase
• 由来する生物種: Methanococcus maripaludis S2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 127524.41

構造登録者

Wagner, T.,Bai, L.,Xu, T.,Hu, X.,Ermler, U.,Shima, S. (登録日: 2017-05-29, 公開日: 2017-07-19, 最終更新日: 2024-01-17)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.75 Å)