Carica papaya (Papaya)
Proteases help digest other proteins by cutting the peptide bond between residues. Through their action they have a multitude of roles, ranging from the digestion of food, reducing proteins to individual amino acids, to the activation of other proteins, thus being involved in the control of cellular processes. Among those some of the most prominent are the serine and the cysteine proteases. Their active sites are similar. Serine proteases use the hydroxyl group of a serine residue and cysteine proteases use the sulfhydryl group of a cysteine residue to help weaken the peptide bond, a process called nucleophilic attack in chemistry. Among the more recent members of the cysteine protease family are the caspases involved in programmed cell death, but the grandfather of all cysteine proteases in structural biology is certainly papain. Papain is contained in the papaya fruit, hence its name indicating its biological origin. It is among the first proteins whose 3-dimensional structure was determined by x-ray crystallography about 40 years ago.
The protein structure is a single polypeptide but divided into two domains. The active site of the protein, formed by residues from both domains, is the typical cleft seen in most proteases. The purpose of this cleft is to provide room for the sidechains of the protein to be cut and help bring the scissile bond, the one that needs to be cut, into the proper position. Proteases become specific for certain types of protein sequences by the shape of this cleft. Papain, like many other cysteine proteases, can be inactivated by oxidation when an oxygen binds to the cysteine sulfur of the active site cysteine. Such an inhibition is irreversible.
Protein Data Bank (PDB)
author: Arno Paehler