ζ-Crystallin, a major cytosolic protein of guinea pig lens, has been characterized as an NADPH: quinone oxidoreductase (EC 220.127.116.11) [Rao et al. (1992) J. Biol. Chem. 267, 97-103]. A bovine lens homolog with 83% sequence identity was found to have very different functional characteristics. While the bovine lens ζ-crystallin exhibits similar physicochemical properties, such as molecular weight, hydropathy profile, and predicted secondary structure, and exhibits strong immunological cross-reactivity with the guinea pig and human lens ζ-crystallins, it shows minimal quinone oxidoreductase activity. On the other hand, bovine lens ζ-crystallin, but not guinea pig ζ-crystallin, showed a strong binding affinity to single-stranded DNA (ssDNA) that could be competed with NADPH, the specific cofactor of ζ- crystallin. NADH and dextran sulfate did not affect this characteristic of bovine ζ-crystallin and the enzyme showed no binding affinity for the heparin-Ultragel A4R. Two-dimensional electrophoresis of bovine lens ζ- crystallin showed a distinct pattern of posttranslational charge modification as compared to the guinea pig protein. Alignment of eight ζ-crystallin sequences, and computer modelling of the bovine and human forms based on the crystallographically analyzed Escherichia coli form, suggest that if loss of a functional residue accounts for the lowered catalytic activity of the bovine protein, Tyr 52 of the E. coli enzyme, and the equivalent Tyr present in all known mammalian forms except the bovine, is the likely candidate. In the bovine form this tyrosine is replaced by histidine.
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