Proline is a nonessential amino acid in the human body. Proline has three forms: DL-proline, L-proline, and D-proline. The proline that is usually referred to is L-proline, a naturally occurring amino acid that is a columnar crystal at room temperature. It quickly decomposes at 215-220℃ when heated. It is soluble in hot water and ethanol, has a slightly sweet taste, and is hygroscopic. It rotates to the left in an alkaline solution. [α]D25-86.5° (water), -60.4° (5N hydrochloric acid). It is found in various proteins. It is a moderately abundant amino acid in marine planktonic organisms and is also present in seawater, particles, and marine sediments.
The unique cyclic structure of the proline side chain gives proline excellent conformational rigidity compared to other amino acids. It also affects the rate of peptide bond formation between proline and other amino acids. When proline is bound to the amide group in a peptide bond, its nitrogen is not bound to any hydrogen, which means it cannot donate hydrogen bonds but can accept hydrogen bonds.
The formation of peptide bonds with incoming Pro-tRNAPro is much slower than with any other tRNA, which is a general feature of N-alkyl amino acids. The formation of the peptide bond between the incoming tRNA and the chain ending in proline is also slow. The formation of the proline-proline bond is the slowest.
The unique conformational rigidity of proline affects the secondary structure of proteins near proline residues and may explain the higher prevalence of proline in thermophilic bacterial proteins. The protein secondary structure can be described by the dihedral angles φ,ψ, and ω of the protein backbone. The cyclic structure of the proline side chain locks the angle φ at about -65°.
Proline can act as a structural disruptor in conventional secondary structure elements like α-helices and β-sheets; however, proline is also commonly found as the xth residue in an α-helix and at the edges of β-sheets. Proline is also common in turns (another secondary structure), helping to form β-turns. This may explain the strange fact that proline is often exposed to solvent despite having a completely nonpolar side chain.
Consecutive prolines or hydroxyprolines can produce polyproline helices, which are the main secondary structure in collagen. Hydroxylation of proline significantly increases the conformational stability of collagen by prolyl hydroxylase. Therefore, proline hydroxylation is a crucial biochemical process for maintaining higher organisms' connective tissues. Severe diseases like scurvy may be caused by defects in this hydroxylation, such as prolyl hydroxylase mutations or a lack of essential ascorbic acid (vitamin C) cofactors.