title: Cysteine is the initial site of modification of alpha-crystallin by kynurenine.
abstract: Tryptophan metabolites, such as kynurenine, are spontaneously unstable at neutral pH. They undergo side-chain deamination yielding reactive alpha, beta unsaturated ketones. In the lens, where these compounds act as UV filters, reaction of the breakdown products with lens proteins (crystallins) may be largely responsible for age-dependent colouration of this tissue. In previous research, where high pH (pH 9) was used to promote deamination and conjugation with lens protein, histidine, lysine, and cysteine residues were found to be modified. In this study we show that, at pH 7, site of reaction with the major lens chaperone alpha-crystallin, is the single cysteine residue of the alphaA subunit. This apparent selectivity has important ramifications because the cysteine-kynurenine adduct is itself unstable under physiological conditions.
authors.affiliation: Australian Cataract Research Foundation, University of Wollongong, Wollongong, New South Wales, 2522, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Aquilina
authors.forename: R J
authors.initials: RJ
authors.lastname: Truscott
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism; D003545:Cysteine; D007737:Kynurenine / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D003459:Crystallins; D007737:Kynurenine; D003545:Cysteine