Aldehyde Reductase: The Role of C-Terminal Residues in Defining Substrate and Cofactor Specificities

The only major structural difference between aldehyde reductase, a primarily NADPH-dependent aldo–keto reductase, and aldose reductase, a dually coenzyme-specific (NADPH/NADH) member of the same superfamily, is an additional eight amino acid residues in the substrate/inhibitor binding site (C-termin...

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Veröffentlicht in:Archives of biochemistry and biophysics 1998-07, Vol.355 (2), p.137-144
Hauptverfasser: Rees-Milton, Karen J., Jia, Zongchao, Green, Nancy C., Bhatia, Mohit, El-Kabbani, Ossama, Flynn, T.Geoffrey
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Sprache:eng
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Zusammenfassung:The only major structural difference between aldehyde reductase, a primarily NADPH-dependent aldo–keto reductase, and aldose reductase, a dually coenzyme-specific (NADPH/NADH) member of the same superfamily, is an additional eight amino acid residues in the substrate/inhibitor binding site (C-terminal region) of aldehyde reductase. On the premise that this segment defines the substrate specificity of the enzyme, a mutant of aldehyde reductase lacking residues 306–313 was constructed. In contrast to wild-type enzyme, the mutant enzyme reduced a narrower range of aldehydes and the new substrate specificity was not similar to aldose reductase as might have been predicted. A major change in coenzyme specificity was observed, however, the mutant enzyme being distinctly NADH preferring(Km, NADH= 35 μM, compared to
ISSN:0003-9861
1096-0384
DOI:10.1006/abbi.1998.0721