Introduction: aspartic peptidases and their clans

This chapter presents an introduction to aspartic peptidases and their clans. Aspartic peptidases are so named because Asp residues are ligands of the activated water molecule. In the great majority of known aspartic peptidases, a pair of aspartic residues act together to bind and activate the catalytic water molecule, but in some, residues of other amino acids replace the second Asp. Aspartic peptidases are assigned to clans AA, AB, AC, AD and AF. Tertiary structures solved for members of clans AA, AB and AF each show a unique protein fold unrelated to that of any other peptidase. For clans AC and AD, there is no crystal structure yet, but other criteria point to their distinctiveness. The clans and the families of aspartic peptidases are summarized in the chapter. The peptidases of family Al are found only in eukaryotes and like all aspartic peptidases, they are endopeptidases. The great majority are most active at acidic pH, but a few show an activity under neutral conditions.