5D4U

SAM-bound HcgC from Methanocaldococcus jannaschii

Summary for 5D4U

• Entry DOI: 10.2210/pdb5d4u/pdb
• Related: 5D4T
• Descriptor: Uncharacterized protein MJ0489, S-ADENOSYLMETHIONINE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: rossmann-like fold, unknown function
• Biological source: Methanocaldococcus jannaschii
• Total number of polymer chains: 4
• Total formula weight: 125395.21

Authors

Fujishiro, T.,Ermler, U.,Shima, S. (deposition date: 2015-08-09, release date: 2016-07-20, Last modification date: 2024-01-10)

Primary citation

Fujishiro, T.,Bai, L.,Xu, T.,Xie, X.,Schick, M.,Kahnt, J.,Rother, M.,Hu, X.,Ermler, U.,Shima, S.
Identification of HcgC as a SAM-Dependent Pyridinol Methyltransferase in [Fe]-Hydrogenase Cofactor Biosynthesis.
Angew.Chem.Int.Ed.Engl., 55:9648-9651, 2016

PubMed Abstract: Previous retrosynthetic and isotope-labeling studies have indicated that biosynthesis of the iron guanylylpyridinol (FeGP) cofactor of [Fe]-hydrogenase requires a methyltransferase. This hypothetical enzyme covalently attaches the methyl group at the 3-position of the pyridinol ring. We describe the identification of HcgC, a gene product of the hcgA-G cluster responsible for FeGP cofactor biosynthesis. It acts as an S-adenosylmethionine (SAM)-dependent methyltransferase, based on the crystal structures of HcgC and the HcgC/SAM and HcgC/S-adenosylhomocysteine (SAH) complexes. The pyridinol substrate, 6-carboxymethyl-5-methyl-4-hydroxy-2-pyridinol, was predicted based on properties of the conserved binding pocket and substrate docking simulations. For verification, the assumed substrate was synthesized and used in a kinetic assay. Mass spectrometry and NMR analysis revealed 6-carboxymethyl-3,5-dimethyl-4-hydroxy-2-pyridinol as the reaction product, which confirmed the function of HcgC.

PubMed: 27391308
DOI: 10.1002/anie.201604352

Experimental method

X-RAY DIFFRACTION (2 Å)