Haiching Ma

TL;DR: The kinetic parameters, steroid substrate specificity and identities of reaction products were determined for four homogeneous recombinant human 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) isoforms of the aldo-keto reductase (AKR) superfamily and the functional plasticity of these isoforms highlights their ability to modulate the levels of active androgens, oestrogens and progestins.

TL;DR: The active-site arrangement observed in the 3 alpha-HSD ternary complex structure suggests that each positional-specific and stereospecific reaction catalyzed by an HSD requires a particular substrate orientation, the general features of which can be predicted.

TL;DR: It is predicted that AKR1C3 catalyzes an ordered bi bi mechanism, that the rate determining step is k(chem), and that an oxyanion prevails in the transition state, and steroidal-based inhibitors that compete with the steroid product would be desirable.

TL;DR: It is concluded that in 3 alpha-HSD, the time dependence of the change in Trp 86 fluorescence is due to cofactor anchoring, and thus,trp 86 is a distal reporter of this event, and the loop movement that accompanies cofactor binding is spectrally silent.

TL;DR: This study represents an example where sex hormone specificity can be changed at the enzyme level with a resultant shift in k(cat)/K(m) for the desired reaction of 2 x 10(11).