Point mutations at threonine-301 modify substrate specificity of rabbit liver microsomal cytochromes P-450 (laurate (omega-1)-hydroxylase and testosterone 16 alpha-hydroxylase)

Biochemical and Biophysical Research Communications
Y Imai, M Nakamura

Abstract

Thr-301 of cytochrome P-450 (laurate (omega-1)-hydroxylase) was replaced by Ser, Val, Ile, or Asn via site-directed mutagenesis. The Ser-, Val-, and Asn-mutants had lower laurate (omega-1)-hydroxylase activities than the wild-type P-450. The mutation to Ser did not affect caprate (omega-1)-hydroxylase activity and rather increased caprate omega-hydroxylase activity, but the Val- and Asn-mutants could not hydroxylate caprate. The Ile-mutant was devoid of the hydroxylase activities. The mutation also led to changes in the affinities for the fatty acids and exogenous ligands. Replacement of Thr-301 of cytochrome P-450 (testosterone 16 alpha-hydroxylase) by Ser or Val also affected the activities toward testosterone and progesterone in different ways. These findings indicate that residue 301 of the P-450s plays an important role in determining their substrate specificities.

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson

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Citations

Sep 3, 1990·Biochimica Et Biophysica Acta·T EgawaT Kitagawa
Dec 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·M NegishiK Aida
Dec 5, 2002·Archives of Biochemistry and Biophysics·David F V Lewis
Jan 4, 1997·Biochimica Et Biophysica Acta·Y ImaiH Shoun
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·K SaitoI Murakoshi
Aug 1, 1994·Journal of Biomolecular Structure & Dynamics·Grazyna D SzklarzJames R Halpert
Apr 1, 1995·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·D F Lewis
Dec 19, 2002·Drug Metabolism Reviews·Thomas M MakrisStephen G Sligar
Mar 7, 2006·Journal of Biotechnology·Rita Bernhardt
Jan 1, 1993·Drug Metabolism Reviews·L KoymansN P Vermeulen
Jan 1, 1990·Critical Reviews in Biochemistry and Molecular Biology·F P Guengerich
Aug 25, 2000·The Journal of Biological Chemistry·H XiangP R Ortiz De Montellano
Dec 13, 1996·The Journal of Biological Chemistry·G EggertsenI Björkhem
Feb 6, 2021·Journal of Personalized Medicine·Masaki KumondaiMasahiro Hiratsuka
Dec 15, 1995·The Journal of Biological Chemistry·G StapletonR Lathe
Jan 24, 1998·Archives of Biochemistry and Biophysics·G Truan, J A Peterson

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Next ❯

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