Steve Ealick's Research Group

2-Methyl-3-Hydroxypyridine-5-Carboxylic Acid Oxygenase

PDB files:




2-Methyl-3-hydroxypyridine-5-carboxylic acid oxygenase (MHPCO), is a flavin-dependent enzyme and catalyzes the oxidative ring opening of 2-methyl-3-hydroxypyridine-5-carboxylic acid to form E-2-acetaminomethylene succinate in a newly discovered vitamin B6 degradative pathway. MHPCO is a flavin-dependent monooxygenase , but also catalyzes a pyridine ring-opening reaction, which is unusual for an enzyme of the monooxygenase family because most oxidative ring-opening reactions of aromatic compounds are catalyzed by iron dependent dioxygenases.

MHPCO shows strong structural similarity to other members of the flavin-dependent hydroxylase family. MHPCO comprises three domains exhibiting mixed α/β folds.


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Two protomers are found within the asymmetric unit lying antiparallel to each other and the dimer spans approximately 75 Å. The two active sites are independent of each other, but face in the same direction and are located more than 40 Å apart.

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The FAD molecule binds within a long cleft roughly 30 Å long and 15 Å wide. FAD is tightly bound in a non-covalent fashion and copurified with the enzyme. Each protomer within the asymmetric unit contains a bound FAD molecule.

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McCulloch KM, Mukherjee T, Begley TP and Ealick SE. Structure of the PLP Degradative Enzyme 2-Methyl-3-hydroxypyridine-5-carboxylic acid Oxygenase from Mesorhizobium loti MAFF303099 and its Mechanistic Implications. Biochemistry 48, 4139-4149 (2009).

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