Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 493, Issue 1, Pages 62-70Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.08.021
Keywords
Pyridoxine; Hydroxypyridine; Hydroxynicotinic acid; Ring-opening; Ring-cleavage; Hydroxylase; Monooxygenase; C4a-hydroperoxy flavin; C4a-hydroxy flavin; Hydroxylation
Categories
Funding
- Thailand Research Fund [BRG5180002]
- Faculty of Science, Mahidol University
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2-Methyl-3-hydroxypyridine-5-carboxylic acid (MHPC) oxygenase (MHPCO) and 5-pyridoxic acid oxygenase are flavoenzymes catalyzing an aromatic hydroxylation and a ring-cleavage reaction. Both enzymes are involved in biodegradation of vitamin B6 in bacteria. Oxygen-tracer experiments have shown that the enzymes are monooxygnases since only one atom of molecular oxygen is incorporated into the products. Kinetics of MHPCO has shown that the enzyme is similar to single-component flavoprotein hydroxylases in that the binding of MHPC is required prior to the flavin reduction by NADH, and C4a-hydroperoxy-FAD and C4a-hydroxy-FAD are found as intermediates. Investigation on the protonation status of the substrate upon binding to the enzyme has shown that only the tri-ionic form of MHPC is bound at the MHPCO active site. Using a series of FAD analogues with substituents at the 8-position of the isoalloxazine ring, the oxygenation of MHPC by the C4a-hydroperoxy-FAD was shown to occur via an electrophilic aromatic substitution mechanism. Recently. the X-ray structures of MHPCO and a complex of MHPC-MHPCO at 2.1 angstrom have been reported and show the presence of nine water molecules in the enzyme active site. Based on structural data, a few residues, Tyr82, Tyr223, Arg181, were suggested to be important for catalysis of MHPCO. (C) 2009 Elsevier Inc. All rights reserved.
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