Functional and conformational modulation of human cytochrome P450 1B1 by anionic phospholipids
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作者:
Jang, Hyun-Hee
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Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South KoreaChonnam Natl Univ, Dept Biochem, Coll Vet Med, Kwangju 500757, South Korea
Jang, Hyun-Hee
[2
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Kim, Dong-Hyun
[2
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Ahn, Taeho
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Chonnam Natl Univ, Dept Biochem, Coll Vet Med, Kwangju 500757, South KoreaChonnam Natl Univ, Dept Biochem, Coll Vet Med, Kwangju 500757, South Korea
Ahn, Taeho
[1
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Yun, Chul-Ho
[2
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[1] Chonnam Natl Univ, Dept Biochem, Coll Vet Med, Kwangju 500757, South Korea
[2] Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South Korea
We investigated the interaction Of human P450 1B1 (CYP1B1)with various phospholipid bilayers using the N-terminally deleted (Delta 2-4)CYP1B1 and (Delta 2-26)CYP1B1 enzymes. Among anionic phospholipids, phosphatidic acid (PA) and cardiolipin specifically increased the catalytic activities, membrane binding affinities, and thermal stabilities of both CYP1B1 proteins when phosphatidylcholine matrix was gradually replaced with these anionic phospholipids. PA- or cardiolipin-dependent changes of CYP1B1 conformation were revealed by altered Trp fluorescence and CD spectra. However, both PA and cardiolipin exerted more significant effects with the (Delta 2-4)CYP1B1 than the (Delta 2-26)CYP1B1 implying the functional importance of N-terminal region for the interaction with the phospholipid membranes. In contrast, other anionic phospholipids such as phosphatidylserine and the neutral phospholipid phosphatidylethanolamine had no apparent effects on the catalytic activity or conformation of CYP1B1. These data suggest that the chemical and physical properties of membranes influenced by PA or cardiolipin composition are critical for the functional roles of CYP1B1. (C) 2009 Elsevier Inc. All rights reserved.
机构:
CHU Quebec, Res Ctr, Endocrinol & Nephrol Unit, Lab Med Chem, Quebec City, PQ, Canada
Univ Laval, Fac Med, Dept Mol Med, Quebec City, PQ, CanadaCHU Quebec, Res Ctr, Endocrinol & Nephrol Unit, Lab Med Chem, Quebec City, PQ, Canada
Dutour, Raphael
Poirier, Donald
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CHU Quebec, Res Ctr, Endocrinol & Nephrol Unit, Lab Med Chem, Quebec City, PQ, Canada
Univ Laval, Fac Med, Dept Mol Med, Quebec City, PQ, CanadaCHU Quebec, Res Ctr, Endocrinol & Nephrol Unit, Lab Med Chem, Quebec City, PQ, Canada