Abstract
Human Class 1 and Class 2 aldehyde dehydrogenases have been sequenced at both the protein (Hempel et al., 1984, 1985) and DNA level (Hsu et al., 1988, 1989). Studies on the tertiary structure of aldehyde dehydrogenase are in progress (Baker et al., 1995, sheep Class 1; Hurley and Weiner, 1992, beef Class 2), but are not sufficiently advanced to suggest which amino acid residues are important in catalysis. Cys 302 is the only completely conserved cysteine in all known forms of the enzyme (Hempel et al., 1993), and labelling by various substrates and substrate analogues (von Bahr-Lindstrom et al., 1985; Kitson et al., 1991; Pietruszko et al., 1993) has implicated this residue as the probable active site nucleophile. This has been confirmed for the Class 2 enzyme by site-directed mutagenesis (Weiner et al., 1991). In order to establish whether Cys 302 is also the active site nucleophile for Class 1 aldehyde dehydrogenase we decided to carry out mutagenesis at Cys 302. A separate mutant was constructed in which Cys 301, the adjacent residue, was changed to alanine while Cys 302 was left unchanged.
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Jones, K.M., Kitson, T.M., Kitson, K.E., Hardman, M.J., Tweedie, J.W. (1995). Human Class 1 Aldehyde Dehydrogenase. In: Weiner, H., Holmes, R.S., Wermuth, B. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 5. Advances in Experimental Medicine and Biology, vol 372. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1965-2_3
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DOI: https://doi.org/10.1007/978-1-4615-1965-2_3
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