Proline
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Proline |
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| Systematic (IUPAC) name | |
| (S)-Pyrrolidine-2- carboxylic acid | |
| Identifiers | |
| CAS number | 147-85-3 |
| PubChem | 614 |
| Chemical data | |
| Formula | C5H9NO2 |
| Molar mass | 115.13 |
| SMILES | OC(=O)[C@@H]1CCCN1 |
| Complete data | |
Proline (abbreviated as Pro or P) is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that humans can synthesize it. It is unique among the 20 protein-forming amino acids because the α-amino group is secondary.
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[edit] Biosynthesis
Proline is biosynthetically derived from the amino acid L-glutamate and its immediate precursor is the imino acid (S)-1-pyrroline-5-carboxylate (P5C). Enzymes involved in a typical biosynthesis include:[1]
- Glutamate kinase (ATP-dependent)
- Glutamate dehydrogenase (requires NADH or NADPH)
- Pyrroline-5-carboxylate reductase (requires NADH or NADPH)
[edit] Structural properties
The distinctive cyclic structure of proline's side chain locks its φ backbone dihedral angle at approximately -75°, giving proline an exceptional conformational rigidity compared to other amino acids. Hence, proline loses less conformational entropy upon folding, which may account for its higher prevalence in the proteins of thermophilic organisms. Proline acts as a structural disruptor in the middle of regular secondary structure elements such as alpha helices and beta sheets; however, proline is commonly found as the first residue of an alpha helix and also in the edge strands of beta sheets. Proline is also commonly found in turns, which may account for the curious fact that proline is usually solvent-exposed, despite having a completely aliphatic side chain. Because proline lacks a hydrogen on the amide group, it cannot act as a hydrogen bond donor, only as a hydrogen bond acceptor.
Multiple prolines and/or hydroxyprolines in a row can create a polyproline helix, the predominant secondary structure in collagen. The hydroxylation of proline by prolyl hydroxylase (or other additions of electron-withdrawing substituents such as fluorine) increases the conformational stability of collagen significantly. Hence, the hydroxylation of proline is a critical biochemical process for maintaining the connective tissue of higher organisms. Severe diseases such as scurvy can result from defects in this hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary ascorbate (vitamin C) cofactor.
Sequences of proline and 2-aminoisobutyric acid (Aib) also form a helical turn structure[citation needed].
In 2006, scientists at ASU discovered that solutions of TiO2 illuminated with ultraviolet radiation can serve as an extremely cost-effective and accurate protein cleavage catalyst. The TiO2 catalyst preferentially and rapidly cleaves protein at sites where proline is present, while taking much longer to degrade the protein from its endpoints.[2]
[edit] Cis-trans isomerization
Peptide bonds to proline and other N-substituted amino acids (such as sarcosine; symbol is X, as is true for all non-standard amino acids) are able to populate both the cis and trans isomers. Most peptide bonds prefer overwhelmingly to adopt the trans isomer (typically 99.9% under unstrained conditions), chiefly because the amide hydrogen (trans isomer) offers less steric repulsion to the preceding Cα atom than does the following Cα atom (cis isomer). By contrast, the cis and trans isomers of the X-Pro peptide bond both experience steric clashes with the neighboring subtitution and are nearly equally energetically disfavorable. Hence, the fraction of X-Pro peptide bonds in the cis isomer under unstrained conditions ranges from 10-40%; the fraction depends slightly on the preceding amino acid, with aromatic residues favoring the cis isomer slightly.
From a kinetic standpoint, Cis-trans proline isomerization is a very slow process that can impede the progress of protein folding by trapping one or more proline molecules crucial for folding in the non-native isomer, especially when the native protein requires the cis isomer. This is because proline residues are exclusively synthesized in the ribosome as the trans isomer form. All organisms possess prolyl isomerase enzymes to catalyze this isomerization, and some bacteria have specialized prolyl isomerases associated with the ribosome. However, not all prolines are essential for folding, and protein folding may proceed at a normal rate despite having non-native conformers of many X-Pro peptide bonds.
[edit] Usage
Proline and its derivatives are often used as asymmetric catalysts in organic reactions. The CBS reduction and proline catalysed aldol condensation are prominent examples.
L-Proline is osmoprotectant and therfore is used in many pharmaceutical, biotechnological applications. For example as an osmoprotectant in the infusions.
L-proline is an ingredient in energy drinks such as "Sobe power fruit punch". [3] Proline has a sweet flavor with a distinct aftertaste.
[edit] See also
- Collagen
- Polyproline helix
- Peptide bond (for more discussion of cis-trans isomerization)
- Hyperprolinemia
[edit] External links
[edit] Notes
- ^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.
- ^ B. J. Jones, M. J. Vergne, D. M. Bunk, L. E. Locascio and M. A. Hayes (2007). "Cleavage of Peptides and Proteins Using Light-Generated Radicals from Titanium Dioxide". Anal. Chem. 79 (4): 1327-1332. doi:.
- ^ http://www.sobebev.com/product_info/powerline_power.shtml beverage has 25mg of Proline.
[edit] References
- Balbach J, Schmid FX. (2000). Proline isomerization and its catalysis in protein folding. In Mechanisms of Protein Folding 2nd ed. Editor RH Pain. Oxford University Press.
- For a thorough scientific overview of disorders of proline and hydroxyproline metabolism, one can consult chapter 81 of OMMBID Charles Scriver, Beaudet, A.L., Valle, D., Sly, W.S., Vogelstein, B., Childs, B., Kinzler, K.W. (Accessed 2007). The Online Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill. - Summaries of 255 chapters, full text through many universities. There is also the OMMBID blog.
- For more online resources and references, see inborn errors of metabolism.
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