In crystallo posttranslational modification within a MauG/pre-methylamine dehydrogenase complex.

Area of Science:

• Biochemistry
• Structural Biology
• Enzymology

Background:

• Methylamine dehydrogenase (MADH) requires a tryptophan tryptophylquinone (TTQ) cofactor for activity.
• MauG is a diheme enzyme essential for the posttranslational modification of tryptophan residues to form the TTQ cofactor.

Purpose of the Study:

• To elucidate the structural basis of MauG-mediated TTQ cofactor synthesis.
• To investigate the catalytic mechanism of MauG in complex with its substrate preMADH.

Main Methods:

• X-ray crystallography was used to determine the structure of the MauG-preMADH complex at 2.1 angstrom resolution.
• Catalytic activity assays were performed by monitoring TTQ synthesis upon addition of hydrogen peroxide.

Main Results:

• The crystal structure revealed significant distances between the c-type heme irons and the TTQ precursor site, implying long-range electron transfer.
• An atypical His-Tyr axial ligation was observed for one of the heme groups.
• The MauG-preMADH complex demonstrated catalytic competence, with MauG-dependent TTQ synthesis occurring in the presence of hydrogen peroxide.

Conclusions:

• The structural and functional data provide insights into the electron transfer pathways and unique ligation in MauG.
• MauG is catalytically active in its crystalline complex, supporting its role in TTQ cofactor formation.