Structure-function Relationship of Proteins

The functions of proteins are maintained becauseof their ability to recognize and interact with a variety of molecules. The three dimensional structural conformation provides and maintains the functional characteristics. The three dimensional structure, in turn, is dependent on the primary structure. So, any difference in the primary structure may produce a protein which cannot serve its function. To illustrate the structure-function relationship, the following three proteins are considered; each belongs to a different class in the functional classification.

Enzymes

The first step in enzymatic catalysis is the binding of the enzyme to the substrate. This, in turn, depends on the structural conformation of the active site of the enzyme, which is precisely
oriented for substrate binding. Carbonic anhydrase catalyses the reversible hydration of carbon dioxide. This enzyme makes it possible for the precise positioning of the CO₂ molecule and the hydroxyl (OH–) ion for the formation of bicarbonate ion. The zinc ion is located at a deep cleft coordinated to histidine residues. The CO₂ binding residues are very near to the zinc ion. Water binds to zinc ion, gets ionized to hydroxyl ion and it binds to the CO₂ which is proximally located. The substrates are brought in close proximity for the reaction to proceed.

Transport proteins

Hemoglobin, the transporter of oxygen is a tetrameric protein (alpha2, beta2), with each monomer having a heme unit. Binding of oxygen to one heme facilitates oxygen binding by other subunits. Binding of H⁺and CO₂ promotes release of O₂ from hemoglobin. This allosteric interaction is physiologically important, and is termed as Bohr effect. Even a single amino acid substitution alters the structure and thereby the function. For example, in sickle cell anemia (HbS), the 6^th amino acid in the beta chain is altered, leading to profound clinical manifestations.

Structural proteins

Collagen is the most abundant protein in mammals and is the main fibrous component of skin, bone, tendon, cartilage and teeth. Collagen forms a super-helical cable where the 3 polypeptide chains are wound around itself. In collagen, every 3rd residue is a glycine. The only amino acid that can fit into the triple stranded helix is glycine. The triple helix of collagen is stabilized by the steric repulsion of the rings of hydroxyproline and also by the hydrogen bonds between them. In vitamin C deficiency, failure of hydroxylation of proline/lysine leads to reduced hydrogen bonding and consequent weakness of collagen. The quarter staggered triple helical structure of collagen is responsible for its tensile strength.