Abstract
The crystal structures of a substrate, an acetylenic suicide substrate, and an allenic inhibitor of the enzyme Δ5-3-keto steroid isomerase of Pseudomonas testosteroni (EC 5.3.3.1) have been determined. The enzyme catalyzes intramolecular proton transfer from C(4) to C(6), converting Δ5- to Δ4-3-keto steroids. The overall conformations of the acetylenic and allenic seco steroids are very much like those of substrate and product. Detailed three-dimensional parameters are given. These studies, together with the known structure of the Δ4-3-keto steroid product have led to some suggestions on the mechanisms of this enzyme. It is proposed that binding of the C-3 carbonyl group of substrate to the enzyme ensures the correct conformation of the A and B rings for 4β hydrogen abstraction, leading to a Δ3,5-dienol. The conformations of the A and B rings will then dictate whether or not a proton is added at C(6) rather than at C(4). The acetylenic seco steroid is thought to bind in a similar manner and is converted enzymatically to the allenic seco steroid, which then alkylates and so inactivates the enzyme.
Original language | English |
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Pages (from-to) | 4282-4289 |
Number of pages | 8 |
Journal | Journal of the American Chemical Society |
Volume | 100 |
Issue number | 13 |
DOIs | |
State | Published - 1978 |