Cysteine Proteases

The Cysteine Proteases - III

Cathepsins are lysosomal enzymes. At least a dozen have been identified, two of which are aspartyl proteases; the rest are cysteine proteases. Their specific functions are still being discovered; they include:

Processing of proenzymes and prohormones
Cartilage reconstruction; abnormal amounts may be related to osteoarthritis and rheumatoid arthritis
Bone reconstruction; defects may lead to osteoporosis
Tumors have abnormally high cathepsin concentrations; cathepsin B is a marker for breast cancer

Although sequence relations are not high (16% identity, 23% similarity for human cathepsin B and papain), structural homology is significant. Rat cathepsin B, for example, has a backbone rmsd of 1.24 A with papain:

Superposition of Cathepsin B and Papain

The catalytic site is located in a deep cleft in the protein, and the catalytic residues are a Cys, His, and Asn, just as in papain:

Cathepsin B from Rat (1cpj)	Catalytic Site

Like all proteases, the cathepsins are born as proenzymes; some undergo autocatalytic activation, others are activated by other proteases. In cathepsin B, the first 63 residues form a large loop that slots into the active site cleft:

Superposition of Cathepsin (red) and Procathepsin (blue)	Activation Loop in Catalytic Site

This page last modified 3:38 PM on Monday April 6th, 2009.
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