Proteases universally recognize beta strands in their active sites

One way to combat infectious diseases is to selectively inhibit foreign proteases within host cells, thus retarding replication rates of infectious organisms and assisting normal immunological defense mechanisms involved in their eradication. This review gives a summary of over 1500 three dimensional crystal (X-ray) and solution (NMR) structures from the pdb of substrates, products and inhibitors bound in the active sites of aspartic, serine, metallo, cysteine, and threonine endopeptidases. These active sites of all five protease classes recognize peptidic and non-peptidic ligands in an extended beta strand conformation, with few exceptions. Comparisons of protease-bound ligand conformations are illustrated by structural superpositions for a subset of structures, including 21 aspartic, 44 serine, 20 metallo, 23 cysteine, and 2 threonine proteases, among the protease-ligand structures analyzed. The extended substrate-binding mode is also illustrated for 3 aspartic proteases, 1 serine protease, 1 cysteine protease and 1 metalloprotease.