title: Structural control of cytochrome P450-catalyzed ω-hydroxylation.
abstract: The regiospecific or preferential ω-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 ω-hydroxylation and our current understanding of the structural features that promote the ω-hydroxylation of unbranched and methyl-branched hydrocarbon chains. The evidence indicates that steric constraints are used to favor reaction at the ω-site rather than at the more reactive (ω-1)-site.
authors: Department of Pharmaceutical Chemistry, University of California-San Francisco, CA 94158-2517, United States.
authors: Jonathan B
authors: JB
authors: Johnston
authors: Hugues
authors: H
authors: Ouellet
authors: Larissa M
authors: LM
authors: Podust
authors: Paul R
authors: PR
authors: Ortiz de Montellano
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008958:Models, Molecular; D015394:Molecular Structure; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D003577:Cytochrome P-450 Enzyme System