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  • Writer's pictureMaciej Szaleniec

Mechanism of enzymatic dehydrogenation of ketosteroids confirmed by our scientists

After more than 50 years of research, the mechanistic hypothesis on steroid dehydrogenation by ketosteroid dehydrogenases has found reconciliation with kinetic studies conducted by Jerussi and Ringold [Biochemistry 1965, 4 (10)].

The joint study of scientists from ICSC PAS, IP PAS, Faculty of Chemistry JU and Universitat Jaume I in Spain published in ACS Catalysis showed that the postulated mechanism is valid despite seemingly contradictory results of kinetic isotope effect (KIE) measured over 50 years ago.

The understanding of the Δ1-dehydrogenation mechanism has not only fundamental value but also a practical one - ketosteroid Δ1-dehydrogenases are important catalysts in the synthesis of various steroid drugs. With a working theoretical model, we will be better prepared for the modification of the activity and specificity of these important catalysts.

The results of modeling showed that the lower value of the observed KIE (1.5–3.5) by the nature of the free energy surface, the presence of diffusion limitation, and to a smaller extent, conformational changes of the enzyme upon substrate binding. We also confirmed that tyrosyl ion acts as the catalytic base and is necessary for efficient activation of the steroid.

Additionally to the Open Access paper, we have deposited Open Data within Mendeley Data repository.

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