Chymopapain

Chymopapain (EC 3.4.22.6, chymopapain A, chymopapain B, chymopapain S, brand name Chymodiactin) is a proteolytic enzyme isolated from the latex of papaya (Carica papaya). It is a cysteine protease which belongs to the PLCP group. Because of its proteolytic activity, it is the main molecule in the process of chemonucleolysis, used in some procedures like the treatment of herniated lower lumbar discs in the spine by a nonsurgical method. Chymopapain (EC 3.4.22.6, chymopapain A, chymopapain B, chymopapain S, brand name Chymodiactin) is a proteolytic enzyme isolated from the latex of papaya (Carica papaya). It is a cysteine protease which belongs to the PLCP group. Because of its proteolytic activity, it is the main molecule in the process of chemonucleolysis, used in some procedures like the treatment of herniated lower lumbar discs in the spine by a nonsurgical method. Chymopapain's zymogen is made up of a total of 352 residues, and it has a weight of approximately 23.78kDa. Three different regions can be distinguished inside the precursor's chain. Chymopapain's structure was solved by X-ray diffraction techniques. Analysis of this structure showed chymopapain to have 7 alpha helix regions, 10 beta sheet regions and 2 loop turns. These 2 turns are the main difference between chymopapain's structure and other papaya proteinase proteins such as papain or caricain, which have similar conformations. Besides, chymopapain presents 3 disulfide bonds as post-traducional modifications stablished between residues 156-197, 190-229 and 287-338. Chymopapain presents a quaternary structure characterized by the formation of homo dimers, which means that two chymopapain chains join each other through weak interactions to conform one unique biological structure. As well as all the other enzymes in the PLCPs group, chymopapain is a cysteine protease. Proteases are enzymes that hydrolyse peptide bonds between the residues that conform a protein. In every hydrolysis a water molecule is released. Specifically, a cysteine protease is an enzyme which breaks the peptide bond by using the thiol group of a cysteine residue as the nucleophile. In order to hydrolyse, the whole catalytic triad of the enzyme must be used. This is constituted by a cysteine, the Cys159 residue, a histidine, the His203 residue, and a third residue, which tens to be a asparagine, specifically the Asn313 residue. The functional groups used in the reaction are the thiol group of the cysteine and the imidazolium ring of a histidine. The asparagine residue works orientating the imidazolium ring of the histidine. The mechanism followed is exposed below: