TY - JOUR
T1 - Irreversible Inhibitors of Δ5-3-Ketosteroid Isomerase
T2 - Acetylenic and Allenic 3-Oxo-5,10-Secosteroids
AU - Batzold, F. H.
AU - Benson, Ann M.
AU - Covey, Douglas F.
AU - Robinson, C. H.
AU - Talalay, Paul
N1 - Funding Information:
These studies were supported by U.S. Public Health Service Research Grants AM 15918, AM 07422, CA 16418 and Training Grant GM 01183.
PY - 1977/1/1
Y1 - 1977/1/1
N2 - The Δ-3-ketosteroid isomerase (EC 5.3.3.1) of Pseudomonas testosterone catalyzes the conversion of a variety of unconiugated Δ 5(6)- and Δ -3-ketosteroids into the corresponding Δ-3-ketosteroids. Typical examples of the reaction are the conversion of Δ-androstene-3,17-dione and Δ-pregnene-3,20-dione to the respective Δ -3-ketosteroids. Considerable information is available on the molecular properties of this enzyme, on the catalytic mechanism, and on the stereochemistry of the enzymic reaction. Based on the proposed molecular mechanism of this reaction, a series of acetylenic 5,10-secosteroids has been prepared in the belief that they might serve as substrates for Δ 5-3-ketosteroid isomerase. Abstraction of the proton at C-4 by the enzyme should then generate, via an enolic intermediate, the corresponding highly reactive conjugated allenic ketones, which might be expected to react covalently with a nucleophilie amino acid residue at the active site. This chapter is based on expected conformational similarities between the acetylenie 5,10-secosteroids and the normal Δ-3-ketosteroid substrates for the enzyme.
AB - The Δ-3-ketosteroid isomerase (EC 5.3.3.1) of Pseudomonas testosterone catalyzes the conversion of a variety of unconiugated Δ 5(6)- and Δ -3-ketosteroids into the corresponding Δ-3-ketosteroids. Typical examples of the reaction are the conversion of Δ-androstene-3,17-dione and Δ-pregnene-3,20-dione to the respective Δ -3-ketosteroids. Considerable information is available on the molecular properties of this enzyme, on the catalytic mechanism, and on the stereochemistry of the enzymic reaction. Based on the proposed molecular mechanism of this reaction, a series of acetylenic 5,10-secosteroids has been prepared in the belief that they might serve as substrates for Δ 5-3-ketosteroid isomerase. Abstraction of the proton at C-4 by the enzyme should then generate, via an enolic intermediate, the corresponding highly reactive conjugated allenic ketones, which might be expected to react covalently with a nucleophilie amino acid residue at the active site. This chapter is based on expected conformational similarities between the acetylenie 5,10-secosteroids and the normal Δ-3-ketosteroid substrates for the enzyme.
UR - http://www.scopus.com/inward/record.url?scp=0017324169&partnerID=8YFLogxK
U2 - 10.1016/S0076-6879(77)46055-5
DO - 10.1016/S0076-6879(77)46055-5
M3 - Article
C2 - 909438
AN - SCOPUS:0017324169
SN - 0076-6879
VL - 46
SP - 461
EP - 468
JO - Methods in Enzymology
JF - Methods in Enzymology
IS - C
ER -