An active-site-directed irreversible inhibitor of Δ5-3-ketosteroid isomerase

Ralph M. Pollack, Robert H. Kayser, Charles L Bevins

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The α and β isomers of spiro-3-oxiranyl-5α-androstan-17β-ol were tested as possible inhibitors of Δ5-3-ketosteroid isomerase of Pseudomonas testosteroni. The β-oxirane causes a first-order irreversible inactivation of the enzyme and shows saturation kinetics (KI, 17 μM). Protection against inactivation is exhibited by 19-nortestosterone, a competitive inhibitor of the isomerase. Although the α-oxirane was found to be a good reversible inhibitor (Ki, 21 μM), prolonged incubation with it failed to produce any inactivation of the isomerase. The results obtained are consistent with the presence of a nucleophilic group situated near the 3-keto group of the substrate in the enzyme-steroid complex.

Original languageEnglish (US)
Pages (from-to)783-790
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume91
Issue number3
DOIs
StatePublished - Dec 14 1979
Externally publishedYes

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steroid delta-isomerase
Ethylene Oxide
Isomerases
Catalytic Domain
Comamonas testosteroni
Nandrolone
Enzymes
Isomers
Steroids
Kinetics
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

An active-site-directed irreversible inhibitor of Δ5-3-ketosteroid isomerase. / Pollack, Ralph M.; Kayser, Robert H.; Bevins, Charles L.

In: Biochemical and Biophysical Research Communications, Vol. 91, No. 3, 14.12.1979, p. 783-790.

Research output: Contribution to journalArticle

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