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Mechanism‐based probes of the topology and function of fatty acid hydroxylases
Author(s) -
De Montellano Paul R. Ortiz,
Chan William K.,
Tuck Stephen F.,
Kaikaus Raja M.,
Bass Nathan M.,
Peterson Julian A.
Publication year - 1992
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.6.2.1537458
Subject(s) - mechanism (biology) , function (biology) , topology (electrical circuits) , chemistry , mathematics , biology , microbiology and biotechnology , physics , combinatorics , quantum mechanics
The use of three mechanism‐based probes to investigate the topology and function of fatty acid hydroxylases is discussed. 1 ) The observation of protein rather than heme alkylation in the reaction of cytochrome P4504A1 with 10‐undecynoic acid supports the argument that the enzyme circumvents the inherent preference for ω ‐1 hydroxylation by restricting access to the ferryl oxygen. 2 ) The regiochemistry of the ferricyanide‐mediated iron‐to‐nitrogen shift of the cytochrome P450102 (P450 BM‐3 ) phenyl‐iron complex indicates that the active site of this bacterial fatty acid hydroxylase is open primarily above pyrrole ring A of the prosthetic heme group, 3 ) Inhibition of clofibrate‐mediated peroxisome proliferation in cultured rat hepatocytes by inactivation of cytochrome P4504A1 indicates that ω ‐hydroxylation of fatty acids provides a signal for peroxisome proliferation.—Ortiz de Montellano, P. R.; Chan, W. K.; Tuck, S. F.; Kaikaus, R. M.; Bass, N. M.; Peterson, J. A. Mechanism‐based probes of the topology and function of fatty acid hydroxylases. FASEB J. 6: 695‐699; 1992.