Proteases

By Sarika Garg

Proteases are divided into five different groups, depending upon the type of molecule in the groove that carries out the actual work of catalysis. Serine proteases attack the peptide bond of the substrate using the hydroxyl group of the side chain of serine present in the catalytic centre. Threonine proteases act in the similar way. Cysteine proteases use the sulphur-hydrogen bond of a cysteine residue to initiate cleavage of the peptide bond. The acidic carboxyl groups of two aspartyl residues carry out this function in aspartyl proteases. Finally metalloproteases have a tightly bound zinc atom in their catalytic centre. Each of these groups of proteins is specialized to perform certain functions. For example, the coagulation of blood is the responsibility of serine proteases, whereas threonine proteases are essential, in particular, for the functioning of the proteasome, a large barrel-shaped protein-degrading apparatus in the cell. Programmed cell death is brought about by cysteine proteases. Digestion can not occur without aspartyl proteases and a subgroup of metalloproteases is essential for the breakdown and rebuilding of the extracellular matrix.

Proteases do not attack their protein substrates at random. Rather, they display a high degree of specificity. This specificity is not defined by the nature of the catalytic centre alone. On either side of the catalytic centre, there is a series of binding sites that favour particular amino acid in the substrate.    

Fig.: Specificity of protease binding. The specificity of protease binding is not defined solely by the nature of the catalytic centre. On either side of the catalytic centre there is a series of binding sites (S) that favour particular amino acids (P). This level of specificity ensures that proteases carry out their task only when truly needed.

Primary information retrieved from public and private sequencing projects, combined with data from the Merops, InterPro, and Ensembl databases, total of 553 genes have been annotated that encode proteases or protease homologues in the human genome. Mouse genome contains 628 proteases and protease homologues.

                                               Table: The human and mouse protease genes and pseudogenes.

References:

Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., et al., 2001. Initial sequencing and analysis of the human genome. Nature. 409(6822), 860-921.

Pietzsch, J., 2003. Signalling scissors: New perspectives on proteases. Horizon Symposia.

Puente, X.S., Sánchez, L.M., Overall, C.M., López-Otín, C., 2003. Human and mouse proteases: a comparative genomic approach. Nat Rev Genet. 4(7), 544-558.

Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., et al., 2001. The sequence of the human genome. Science. 291(5507), 1304-1351. 

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