Dityrosine, structure

FIGURE 9.3 Cross-linked recombinant resilin. (a) Structure of the dityrosine adduct, (b) A cross-linked moulded rod. (c) HPLC analysis of acid-hydrolyzed uncross-Unked recombinant resilin and cross-linked recombinant resilin. (From Elvin, C.M., Carr, A.G., Huson, M.G., Maxwell, J.M., Pearson, R.D., Vuocolo 1, T., Liyon, N.E., Wong, D.C.C., Merritt, D.J., and Dixon, N.E., Nature, 437, 999, 2005.)... 

In animal structural proteins in vivo, the only known dimer of tyrosine is dityrosine (40,41) in the extensin of plant cell walls, in contrast, the only dimer formed in vivo is isodityrosine (16). How is the coupling of tyrosine in plants confined to the formation of isodityrosine There is nothing unique about the local environment of the tyrosine residues in (pure) extensin, since... 

Figure 4. Structures of tyrosine, dityrosine and isodityrosine. [Reproduced with permission from Journal of Experimental Botany 38, 853-62 Oxford University Press, 1987.

Role of Neighboring Polysaccharide Molecules in Determining the Orientation of Tyrosine Residues During Coupling. These considerations suggest a third possible explanation for the exclusive formation of isodityrosine in the plant cell wall in vivo that the neighboring structural molecules of the wall constrain extensin to prevent dityrosine formation. This would mean that the biologically relevant substrate for peroxidase in the plant cell wall is not naked extensin but extensin complexed with another wall component, possibly an acidic polysaccharide to which the extensin would bind ionically. 

Lygo has extended his asymmetric alkylation methodology to the synthesis of bis-a-amino acids (Scheme 4) [11], Bis-amino acids, such as meso-diaminopirnelic acid, dityrosine and isodityrosine, are found in nature and are thought to act as cross-linking agents which stabilise structural proteins in plants and bacteria. For example, asymmetric alkylation of the Schiff base 3 with the dibromide 13, catalysed by the quaternary ammonium salt le, gave the bis-amino acid derivative 14 in >95% ee. 

More recently, MPO-mediated oxidation of tyrosine to dityrosine (o o -dityrosine, or 3,3 -diiyrosine) focused attention as a marker reaction of neutrophile-dependent oxidative damage of proteins and peptides (G11, H14, S3). The reaction occurs both with free tyrosine as well as with tyrosyl residues incorporated into polypeptide structures. The mechanism of dityrosine formation utilizes a relatively long-lived phenoxyl radical that cross-links to dimeric and polymeric structures by formation of carbon-carbon bonds between the aromatic moieties of phenolic tyrosine residues (H14) (Fig. 9). 

Covalent cross-links between tyrosine residues have been found in the egg coat proteins of certain invertebrates, suggesting the possibility of a structural role for dityrosine in biology. 

Covalent linkage between two amino acid side chains within a single polypeptide chain appears to be a surprisingly coimnon modification that may serve a function in the structure or reactivity of the protein. In addition to the cross-linked o,o -dityrosine dimers vide supra. Section 2.5) and the quinocofactor, LTQ vide supra, Section 3.1.2), a number of other covalent sttuctures have been identified, mainly by X-ray crystallography. These cross-linked amino acid derivatives include cysteinyl-tyrosine (22), histidyl-tyrosine (23), and cysteinyl-histidine (24). 

Castellan et al. [171] have recently suggested that dityrosine protein residues or p-hydroxycinnamic acid are possible candidates for the fluorphores in pure cellulose. Other recent studies [172,173] have shown that typical cellulose processing conditions (e.g., hot alkali) can induce the formation of small amounts of aromatic structures from reducing end groups or hemicelluloses. However, many of the structures identified in these studies are quinones, which are at best weakly fluorescent. 

Yoburn JC, Tian W, Brower JO, Nowick JS, Glabe CG, Van Vranken DL (2003) Dityrosine cross-linked Abeta peptides fibrillar beta-structure in Abeta(l-40) is conducive to formation of dityrosine cross-links but a dityrosine cross-link in Abeta(8-14) does not induce beta-structure. Chem Res Toxicol 16 531-535 Yoder G, Polese A, Silva R, Formaggio F, Crisma M, Broxterman QB, Kamphuis J, Toniolo C, Keiderling TA (1997) Conformational characterization of terminally blocked L-(alpha Me)Val homopeptides using vibrational and electronic circular dichroism. 3(10)-helical stabilization by peptide-peptide interaction. J Am Chem Soc 119 10278-10285... 

Intermediates occurring in these mechanisms have been identified by ESR measurements and by flash photolysis studies using optical absorption detection. For example, ESR measurements on wool keratins revealed the formation of sulfur-centered radicals of the structure RCH2S, which, in this case, are assumed to result from a reaction of electronically excited tyrosine moieties with cystine residues [11]. In many proteins, cross-links are formed. In the case of keratin and collagen, the cross-links are of the tryptophan-histidine and dityrosine types [11]. Cross-links formed by the combination of R-S or R-S-S radicals, both intermolecularly and intramolecularly, with incorrect sites are considered to be an important source of photoaggregation effects [8]. ESR measurements have also yielded evidence of C-H and C-N bond ruptures [8]. 

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