Seven peptidase (proteinase) familiesaspartic,
cysteine,
metallo, serine, glutamic, threonine, and asparagineare in
the peptidase database MEROPS, version 12.4 (). The glutamic peptidase family is assigned two clans, GA and GB,
and comprises six subfamilies. This perspective summarizes the unique
features of their representatives. (1) G1, scytalidoglutamic peptidase,
has a β-sandwich structure containing catalytic residues glutamic
acid (E) and glutamine (Q), thus the name eqolisin. Most family members
are pepstatin-insensitive and act as plant pathogens. (2) G2, preneck
appendage protein, originates in phages, is a transmembrane protein,
and its catalytic residues consist of glutamic and aspartic acids.
(3) G3, strawberry mottle virus glutamic peptidase, originates in
viruses and has a β-sandwich structure with catalytic residues
E and Q. Neprosin has propyl endopeptidase activity, is associated
with celiac disease, has a β-sandwich structure, and contains
catalytic residues E-E and Q-tryptophan. (4) G4, Tiki peptidase, of
the erythromycin esterase family, is a transmembrane protein, and
its catalytic residues are E-histidine pairs. (5) G5, RCE1 peptidase,
is associated with cancer, is a transmembrane protein, and its catalytic
residues are E-histidine and asparagine–histidine. Microcystinase,
a bacterial toxin, is a transmembrane protein with catalytic residues
E-histidine and asparagine–histidine. (6) G6, Ras/Rap1-specific
peptidase, is a bacterial pathogen, a transmembrane protein, and its
catalytic residues are E-histidine pairs. This family’s common
features are that their catalytic residues consist of a glutamic acid
and another (variable) amino acid and that they exhibit a diversity
of biological functionsplant and bacterial pathogens and involvement
in celiac disease and cancerthat suggests they are viable
drug targets.