Aldehyde Dehydrogenase Catalytic Mechanism (original) (raw)

Abstract

Elsewhere in this volume we detail findings from an alignment of 145 ALDH sequences (Perozich et al., 1999), and previously at these meetings we reported that the crystal structure of a class 3 ALDH (E-NAD binary complex) revealed a non-traditional mode of NAD-binding within an open β/α domain otherwise familiar in the NAD-binding “ossmann folds” of other dehydrogenases (Liu et al., 1997a). The variability of residues in the substrate-binding site clearly indicates evolutionary tailoring of the substrate specificities of inddual ALDHs. However, farther to the interior of the active site-between the catalytic thiol and NAD molecule where hydride transfer from aldehyde to NAD occurs-strict conservations are compatible with a common chemical mechanism (Liu et al., 1997b)he position of NAD in an isomorphous class 3 ALDH derivative and the emergence of Asn4/169 as a strictly conserved residue prompted us to consider the catalytic mechanism we present here.

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Authors and Affiliations

1. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA
   John Hempel & John Perozich
2. Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA
   Toby Chapman
3. Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, 30602, USA
   John Rose, Zhi-Jie Liu, Ronald Lindahl & Bi-Cheng Wang
4. Department of Biochemistry and Molecular Biology, University of South Dakota, Vermillion, South Dakota, 57069, USA
   Josette S. Boesch

Authors

1. John Hempel
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2. John Perozich
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3. Toby Chapman
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4. John Rose
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5. Josette S. Boesch
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6. Zhi-Jie Liu
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7. Ronald Lindahl
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8. Bi-Cheng Wang
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Editors and Affiliations

1. Purdue University, West Lafayette, Indiana, USA
   Henry Weiner
2. Philipps University of Marburg, Marburg, Germany
   Edmund Maser
3. Indiana University School of Medicine, Indianapolis, Indiana, USA
   David W. Crabb
4. University of South Dakota School of Medicine, Vermillion, South Dakota, USA
   Ronald Lindahl

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Hempel, J. et al. (1999). Aldehyde Dehydrogenase Catalytic Mechanism. In: Weiner, H., Maser, E., Crabb, D.W., Lindahl, R. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 7. Advances in Experimental Medicine and Biology, vol 463. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4735-8\_7

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• DOI: https://doi.org/10.1007/978-1-4615-4735-8\_7
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