Common protein architecture and binding sites in proteases utilizing a Ser/Lys dyad mechanism

Escherichia coli signal peptidase (SPase) and E. coli UmuD protease are mem bers of an evolutionary dan of serine proteases that apparently utilize a s erine-lysine catalytic dyad mechanism. Recently, the crystallographic struc ture of a SPase inhibitor complex was solved elucidating the catalytic resi dues and the substrate binding subsites. Here we show a detailed comparison of the E. coli SPase structure to the native E. coli UmuD' structure. The comparison reveals that despite a very low sequence identity these function ally diverse enzymes share the same protein fold within their catalytic cor e and allows by analogy for the assignment of the cleavage-site orientation and substrate binding subsites in the UmuD(D') protease. The structural al ignment of SPase and UmuD' predicts important mechanistic and structural si milarities and differences within these newly characterized families of ser ine proteases.