The Aromatic Substrate Binding Site in Subtilisin BPN' and Its Resemblance to Chymotrypsin

Abstract

Many lines of evidence suggest that subtilisin BPN′ or Novo, which are identical (Robertus et al., 1971), and the closely related subtilisin Carlsberg function by a mechanism very similar to that of chymotrypsin and its relatives. In addition, although the specificity of subtilisin is less pronounced than chymotrypsin, it also shows a distinct preference for esters and amides of aromatic or hydrophobic amino acids. X-ray crystallographic studies thus far (Wright et al., 1969; Alden et al., 1970) have shown that although the overall three-dimensional folding of the two enzymes is totally different, there is a remarkable resemblance at the catalytic site. Both contain exactly the same hydrogen bond network, involving Ser 221, His 64 and Asp 32 in subtilisin and Ser 195, His 57 and Asp 102 in chymotrypsin with corresponding side chains in an identical geometrical arrangement. This hydrogen bond network plays a central role in the mechanism proposed...