Molecular basis for the ω-regiospecificity of the CYP4A2 and CYP4A3 fatty acid hydroxylases

Ute Hoch, J R Falck, Paul R. Ortiz De Montellano

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6 Scopus citations


The CYP4A fatty acid ω-hydroxylases are involved in important physiological processes such as the regulation of vascular pressure. A previous study of chimeras of the rat CYP4A2 and CYP4A3 enzymes established that the regiochemistry of fatty acid hydroxylation is determined by the first 119 amino acid residues (Hoch, U., Zhang, Z. P., Kroetz, D. L., and Ortiz de Montellano, P. R. (2000) Arch. Biochem. Biophys. 373, 63-71). The role of the individual amino acid differences in this region has therefore been examined by site-specific mutagenesis to determine which residues actually control the ω-versus (ω-1)-regiospecificity. The results indicate that regiospecificity is controlled by the presence or absence of a three-residue insert (Ser-114, Gly-115, Ile-116) in CYP4A3 and by the residue at position 119 (CYP4A3 numbering). Furthermore, analysis of the absolute stereochemistry of the 11-hydroxylauric acid product indicates that this stereochemistry is not very sensitive to changes in the residues that line the substrate access channel. These results define a model of the specificity determinants of an important class of cytochrome P450 enzymes.

Original languageEnglish (US)
Pages (from-to)26952-26958
Number of pages7
JournalJournal of Biological Chemistry
Issue number35
StatePublished - Sep 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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