InterPro: IPR001096 Peptidase C13, legumain

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

• Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
• Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad or triad [1].

This group of cysteine peptidases belong to the MEROPS peptidase family C13 (legumain family, clan CD). A type example is legumain from Canavalia ensiformis (Jack bean, Horse bean). The blood fluke parasite Schistosoma mansoni has two cysteine proteases in its digestive tract, one a cathepsin B-like protease, the other termed hemoglobinase [2, 3]. The latter has been hard to purify, free of cathepsin B, and expressed forms in Escherichia coli prove to be inactive, suggesting that hemoglobinase may act in association with cathepsin B [2, 4]. Plant vacuolar processing enzyme and legumain from legumes [2] have been shown to have sequence and functional similarity to hemoglobinase. The catalytic residues of the family are currently unknown, but sequence alignments reveal one totally conserved cysteine and two totally conserved histidines.