Six-base deletion occurring in messages of human cytochrome P-450 in the CYP2C subfamily results in reduction of tolbutamide hydroxylase activity

Biochem Int. 1992 Sep;27(6):1073-81.

Abstract

We isolated and expressed a clone, hPA6, possibly corresponding to the CYP2C9 cDNA. Compared with the other CYP2C9 cDNA clones, hPA6 showed a 6-nucleotide deletion near its middle. From the same cDNA library, we could also isolate another cDNA clone, named hPA22, which retained the 6 bases. For clarification of the effect of the 2-amino acid deletion resulting from the 6-base deletion on enzymatic activities, both clones were expressed in yeast. The expressed enzymes showed tolbutamide hydroxylase activities, and these activities were inhibited by antibodies against P-450-HM2, a probable CYP2C9. The activity of the enzyme encoded by hPA6 was lower than that encoded by hPA22; thus the 2-amino acid deletion in the CYP2C9 reduced the enzymatic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Western
  • Cloning, Molecular
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA
  • Humans
  • Microsomes / enzymology
  • Mixed Function Oxygenases / metabolism*
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Plasmids
  • Saccharomyces cerevisiae
  • Sequence Deletion
  • Tolbutamide / metabolism

Substances

  • DNA
  • Cytochrome P-450 Enzyme System
  • Tolbutamide
  • Mixed Function Oxygenases
  • tolbutamide 4-hydroxylase

Associated data

  • GENBANK/M57479
  • GENBANK/M86474
  • GENBANK/M86475
  • GENBANK/M86476
  • GENBANK/M86477
  • GENBANK/M86478
  • GENBANK/M86479
  • GENBANK/M86480
  • GENBANK/M86481
  • GENBANK/S46963