title: Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases.
abstract: We show by site-directed mutagenesis that the catalytic residues of mammalian legumain, a recently discovered lysosomal asparaginycysteine endopeptidase, form a catalytic dyad in the motif His-Gly-spacer-Ala-Cys. We note that the same motif is present in the caspases, aspartate-specific endopeptidases central to the process of apoptosis in animal cells, and also in the families of clostripain and gingipain which are arginyl/lysyl endopeptidases of pathogenic bacteria. We propose that the four families have similar protein folds, are evolutionarily related in clan CD, and have common characteristics including substrate specificities dominated by the interactions of the S1 subsite.
authors.affiliation: MRC Molecular Enzymology Laboratory, Babraham Institute, Cambridge, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Chen
authors.forename: N D
authors.initials: ND
authors.lastname: Rawlings
authors.forename: R A
authors.initials: RA
authors.lastname: Stevens
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D019143:Evolution, Molecular; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010940:Plant Proteins; D017386:Sequence Homology, Amino Acid; D000099240:Asparaginyl Endopeptidase
chemical_list: D018829:Adhesins, Bacterial; D020169:Caspases; D003546:Cysteine Endopeptidases; D017931:DNA Primers; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D010940:Plant Proteins; D000099240:Asparaginyl Endopeptidase; C019913:clostripain