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

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

doi:10.1016/0006-291X(79)91948-X

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

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

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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 (K_I, 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 (K_i, 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 language	English (US)
Pages (from-to)	783-790
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	91
Issue number	3
DOIs	https://doi.org/10.1016/0006-291X(79)91948-X
State	Published - Dec 14 1979
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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10.1016/0006-291X(79)91948-X

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title = "An active-site-directed irreversible inhibitor of Δ5-3-ketosteroid isomerase",

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.",

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T1 - An active-site-directed irreversible inhibitor of Δ5-3-ketosteroid isomerase

AU - Pollack, Ralph M.

AU - Kayser, Robert H.

AU - Bevins, Charles L

PY - 1979/12/14

Y1 - 1979/12/14

N2 - 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.

AB - 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.

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

Abstract

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