Structural control of cytochrome P450-catalyzed ω-hydroxylation

The regiospecific or preferential omega-hydroxylation of hydrocarbon chains is thermodynamically disfavored because the ease of C-H bond hydroxylation depends on the bond strength, and the primary C-H bond of a terminal methyl group is stronger than the secondary or tertiary C-H bond adjacent to it. The hydroxylation reaction will therefore occur primarily at the adjacent secondary or tertiary C-H bond unless the protein structure specifically enforces primary C-H bond oxidation. Here we review the classes of enzymes that catalyze omega-hydroxylation and our current understanding of the structural features that promote the omega-hydroxylation of unbranched and methyl-branched hydrocarbon chains. The evidence indicates that steric constraints are used to favor reaction at the omega-site rather than at the more reactive (omega-1)-site. (C) 2010 Elsevier Inc. All rights reserved.