Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases

FEBS Letters

Stevens, Richard A.E.¹  Rawlings, Neil D.¹  Chen, Jinq-May¹  Barrett, Alan J.¹ 

[1] MRC Molecular Enzymology Laboratory, Babraham Institute, Babraham, Cambridge CB2 4AT, UK

关键词: Legumain;    Caspase;    Clostripain;    Gingipain;    Peptidase clan;   

DOI  :  10.1016/S0014-5793(98)01574-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown