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Steroid delta-isomerase (KSI)

Target
KSI
Molecular classification
Enzyme, Isomerase
01

Overview

Steroid delta-isomerase (KSI) is an enzyme (EC 5.3.3.1) that catalyzes the isomerization of 3-oxo-Δ5-steroids to 3-oxo-Δ4-steroids, a key step in steroid metabolism[1][2]. In bacteria such as *Pseudomonas putida* and *Comamonas testosteroni*, it enables the breakdown of steroid molecules that can be used as carbon sources[2][4]. In mammals, a functionally similar activity is carried out as part of the steroidogenic pathway, but typically by a bifunctional enzyme, 3-beta-hydroxysteroid dehydrogenase/delta-5,4-isomerase. The enzyme works at a diffusion-limited rate and involves a mechanistic base (Asp-99) and multiple hydrophobic residues to position the steroid substrate for catalysis[2][3]. There is ongoing scientific interest in KSI as a model enzyme for studying protein dynamics, catalysis, and structural evolution, rather than as a direct therapeutic target. Caveats and limitations: - The term "Steroid delta-isomerase" most specifically refers to the bacterial enzyme (KSI), not the mammalian bifunctional 3β-HSD/Δ5,4-isomerase[2][6][7]. - There are no well-established clinical drugs specifically targeting this enzyme in humans; interacting drugs listed are experimental or have unknown physiological relevance[4]. - Direct safety concerns or biomarker use in humans have not been established.

Other names
5.3.3.1Delta(5)-3-ketosteroid isomeraseketosteroid isomerase (KSI)3-oxo-Δ5-steroid isomerase
02

Mechanism of action

Catalyzes the isomerization of steroid substrates by facilitating the shift of a double bond from Δ5 to Δ4 position in the steroid nucleus, enabling conversion from 3-oxo-Δ5-steroids to 3-oxo-Δ4-steroids[1][2][5]

03

Biological functions

Steroid metabolismSteroid degradationHormone biosynthesis (in steroidogenic tissues)
04

Disease associations

Other (primarily involved in steroid metabolism in microorganisms and some animal tissues; not directly established in major disease categories such as cancer or neurodegeneration)
05

Interacting drugs

deoxycholic acid

1 more in the full profile.

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