Hydroxyproline structure

FIGURE 4.4 The structures of several atniuo acids that are less cotntnou but nevertheless found in certain proteins. Hydroxylysine and hydroxyproline are found in connective-tissue proteins, pyroglutatnic acid is found in bacteriorhodopsin (a protein in Halohacterium halohium), and atninoadipic acid is found in proteins isolated from corn. 

The tendencies of the amino acids to stabilize or destabilize a-helices are different in typical proteins than in polyamino acids. The occurrence of the common amino acids in helices is summarized in Table 6.1. Notably, proline (and hydroxyproline) act as helix breakers due to their unique structure, which fixes the value of the —N—C bond angle. Helices can be formed from either... 

The amino acids proline and hydroxyproline exert a stabilizing influence on the triple helix as described in detail in Sect. 4.5. By examining the CB peptides of collagen, a structural stability which is directly proportional to the itnino acid content may thus be found. It has, however, not been possible to synthesize model peptides displaying structural stability comparable to that of the native peptides having corresponding amino acid contents. 

Fig. 4. Helical structure of collagen, typical amino acid sequence within a collagen strand, and exchangeable versus non-exchangeable hydrogen atoms in an individual leucine molecule (Gly - glycine. Pro - Proline, Leu - leucine. Hyp - hydroxyproline.

Other workers began to study the structure of gramicidin. Christensen and coworkers12 isolated crystalline tryptophane and leucine from a hydrolysate. They found no evidence for a fatty acid component and established that phenylalanine, proline and hydroxyproline were absent from a hydrolysate. These workers isolated alanine diox-pyridate from a hydrolysate and also established that gramicidin contained a compound with vicinal hydroxy and amino groups. They speculated that this compound might be serine or isoserine and proposed that gramicidin contains two tryptophane, 2 leucine, 2 or 3 alanine and 1 hydroxyamino residues or a multiple of this composition. 

Figure 11.3 The effect of imino acids on protein structure. The presence of the imino acids proline and hydroxyproline introduces a constraint into the angles of the peptide bond which results in a bend in the previously regular chain structure.

The many (possibly more than 30) types of collagens found in human connective tissues have substantially the same chemical structure consisting mainly of glycine with smaller amounts of proline and some lysine and alanine. In addition, there are two unusual amino acids, hydroxyproline and hydroxylysine, neither of which has a corresponding base-triplet or codon within the genetic code. There is therefore, extensive post-translational modification of the protein by hydroxylation and also by glycosylation reactions. 

Although the exact amino acid sequence differs between the various collagens, the primary structure usually conforms to a repeating tripeptide Gly-X-Y where X and Y are, proline, lysine, or hydroxyproline, hydroxylysine respectively. A single unit of collagen is a triple helix composed of three a chains. This conformation differs from the common a helix found in proteins in two important ways ... 

Min, J. H. et al. Structure of an HIF-lalpha-pVHL complex hydroxyproline recognition in signaling. Science 2002, 296, 1886-9. 

So what does this magical molecule do Actually, it does two things, one rather more crystalline clear than the other. The crystal clear thing that ascorbic acid does is act as coenzyme for an enzyme known as prolyl hydroxylase. This enzyme catalyzes the conversion of the amino acid proline to hydroxyproline, a major, if exotic, amino acid in the structural protein collagen ... 

Collagen synthesized in the absence of ascorbic acid (i.e. without hydroxyproline) cannot form its usual stable structure. Collagen is a major component of the structural and connective tissues of the body bone, cartilage, tendons, ligaments, teeth, and skin. Small wonder that things sort of fall apart in the absence of adequate ascorbic acid to support the activity of prolyl hydroxylase. 

Vitamin C is essential for the formation of collagen, the principal structural protein in skin, bone, tendons, and ligaments, being a cofactor in the hydroxylation of the amino acids proline to 4-hydroxyproline, and of lysine to 5-hydroxylysine. These hydroxyamino acids account for up to 25% of the collagen structure. Vitamin C is also associated with some other hydroxylation reactions, e.g. the hydroxylation of tyrosine to dopa (dihydroxyphenylalanine) in the pathway to catecholamines (see Box 15.3). Deficiency leads to scurvy, a condition characterized by muscular pain, skin lesions, fragile blood vessels, bleeding gums, and tooth loss. Vitamin C also has valuable antioxidant properties (see Box 9.2), and these are exploited commercially in the food industries. 

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