Structure and Catalytic Mechanism of 3-Ketosteroid Dehydrogenases |
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| Institution: | 1. Laboratory of Biophysical Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands;2. Department of Chemistry, Faculty of Sciences and Technology, Universitas Airlangga, Kampus C Unair, Jl. Mulyorejo, Surabaya 60115, Indonesia |
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| Abstract: | 3-Ketosteroid dehydrogenases (KSTDs) are FAD-dependent enzymes that introduce a double bond in the A ring of 3-ketosteroid substrates to initiate degradation of the steroid nucleus. Δ1-KSTD desaturates the C1-C2 bond of the steroid, while Δ4-KSTD targets the C4-C5 bond. Crystal structures with bound products showed that Δ1- and Δ4-KSTD use different amino acid residues to catalyze an otherwise mechanistically very similar reaction (Δ1-KSTD: Tyr318, Tyr119, and Tyr487; Δ4-KSTD: Ser468, Tyr319, and Tyr466). However, the substrates are rotated by ∼40° about an axis perpendicular to their plane to bring the target bond (C1-C2 or C4-C5) in the right position. |
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| Keywords: | Steroid degradation dehydrogenase FAD catalytic mechanism ketosteroid cholesterol |
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