Structure and Catalytic Mechanism of 3-Ketosteroid Dehydrogenases

Bauke W. Dijkstra, Niels van Oosterwijk, Ali Rohman
2016 Procedia Chemistry  
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. 1 -KSTD desaturates the C1-C2 bond of the steroid, while 4 -KSTD targets the C4-C5 bond. Crystal structures with bound products showed that 1 -and 4 -KSTD use different amino acid residues to catalyze an otherwise mechanistically very similar reaction ( 1 -KSTD: Tyr318, Tyr119, and Tyr487; 4 -KSTD: Ser468, Tyr319,
more » ... d 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.
doi:10.1016/j.proche.2016.01.006 fatcat:h3lmkxohyvarnkacdog3ld2nrq