Importance of Structure on Function of Proteins

Proteins are the workhorses of cells and in every activity there is the involvement of one or more proteins in different ways. Now, it is very clear that each protein has a specific three-dimensional shape determined by the amino acid sequence and various other intermolecular interactions. This three-dimensional shape has a great influence on the biological function that it performs in the cells. We consider two proteins, as an example, to understand the importance of a three-dimensional structure on its specific function: a proteolytic enzyme, chymotrypsin, and the oxygen carrying protein, hemoglobin.

Chymotrypsin - A Protein- Digesting Enzyme:
Chymotrypsin is a member of a family of enzymes, all of which cleave peptide bonds through the action of an active site serine (the serine proteases). This family includes the pancreatic enzymes chymotrypsin, trypsin, and elastase as well as a variety of other proteases (e.g., cocoonase, thrombin, acrosomal protease, etc.). Chymotrypsin, trypsin, and elastase show a high degree of similarity in their overall tertiary structure, but have different substrate specificities determined by a specific substrate-binding site on each enzyme.

Chymotrypsin is one of the proteinhydrolyzing enzymes produced by the digestive gland pancreas. The protein present in the food that we eat is digested mainly by two proteases - trypsin and chymotrypsin in the beginning of the small intestine (the duodenum). These two digestive enzymes are produced by pancrease and are released into the duodenum through the pancreatic duct. Thus, the site of production of these enzymes is the pancreas and their site action is the duodenum.

Trypsin and chymotrypsin cut the linear polypeptide chains into short peptides by cutting at specific sites. These short pep tides thus produced are acted upon by other peptidases releasing amino acids. But the pancreas is made up of many proteins. How are these proteins protected from the hydrolytic activity of chymotrypsin? These types of hydrolytic enzymes, particularly proteases are produced in an inactive form called zymogen and are transported to the site of action, the duodenum-where it is converted into an active enzyme by a process known as in situ activation. Because of this process, the protein undergoes a major change in its three-dimensional shape, which is now suitable for its interaction with its substrates. The active chymotrypsin enzyme is known as alpha. chymotrypsin and its inactive form from which it is produced is called chymotrypsinogen.

Know the Chymotrypsinogen:
Chymotrypsinogen, the precursor (zymogen) of active chymotrypsin, consists of 245 amino acid residues. Activation of chymotrypsinogen involves proteolytic cleavage at two sites along the chain and removal of two amino acids at each cleavage site. The resultant three peptide chains are A, B, and C. These three chains are held together by five disulfide bonds and fold into a globular structure. This process of folding brings three distantly placed amino acid residues his 57, asp 102, and ser 195 close together in a particular order to form the active center or the reaction center of the enzyme. The overall chymotrypsin molecule is folded into two domains, each containing six beta strands arranged as antiparallel sheets that form a circular structure known as a beta barrel. The active site residues (ser 195, his 57, and asp 102) are far apart in the primary sequence but are brought together in a crevice formed between the two protein domains

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