Fig. 4. Dynamics of SRD5A2 during reaction.

a Dominant conformational motions in the SRD5A2 MD simulations using principal component analysis (PCA). To visualize the motions, two representative conformations from the principal components for the apo and nap states are indicated in orange and blue, respectively. The SRD5A2 crystal structure colored in green is superimposed as a reference. PCA clearly indicates large-scale motions in L1 and L5, suggesting opening up of the nucleotide-binding cavity. b Model of the dynamics of SRD5A2 in one cycle of reaction. The reaction can be inhibited by finasteride by forming a stable adduct with the NADPH cofactor to stabilize the closed conformation of SRD5A2. Testosterone and finasteride are indicated as “T” and “Fina”, respectively. Testosterone catalysis and the finasteride inhibition are shown with black and red arrows, respectively.