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Relationships within the aldehyde dehydrogenase extended family

Published online by Cambridge University Press:  01 January 1999

JOHN PEROZICH
Affiliation:
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
HUGH NICHOLAS
Affiliation:
Pittsburgh Supercomputing Center, Carnegie-Mellon University, Pittsburgh, Pennsylvania 15213
BI-CHENG WANG
Affiliation:
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602
RONALD LINDAHL
Affiliation:
Department of Biochemistry and Molecular Biology, University of South Dakota, Vermillion, South Dakota 57069
JOHN HEMPEL
Affiliation:
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
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Abstract

One hundred-forty-five full-length aldehyde dehydrogenase-related sequences were aligned to determine relationships within the aldehyde dehydrogenase (ALDH) extended family. The alignment reveals only four invariant residues: two glycines, a phenylalanine involved in NAD binding, and a glutamic acid that coordinates the nicotinamide ribose in certain E-NAD binary complex crystal structures, but which may also serve as a general base for the catalytic reaction. The cysteine that provides the catalytic thiol and its closest neighbor in space, an asparagine residue, are conserved in all ALDHs with demonstrated dehydrogenase activity. Sixteen residues are conserved in at least 95% of the sequences; 12 of these cluster into seven sequence motifs conserved in almost all ALDHs. These motifs cluster around the active site of the enzyme. Phylogenetic analysis of these ALDHs indicates at least 13 ALDH families, most of which have previously been identified but not grouped separately by alignment. ALDHs cluster into two main trunks of the phylogenetic tree. The largest, the “Class 3” trunk, contains mostly substrate-specific ALDH families, as well as the class 3 ALDH family itself. The other trunk, the “Class 1/2” trunk, contains mostly variable substrate ALDH families, including the class 1 and 2 ALDH families. Divergence of the substrate-specific ALDHs occurred earlier than the division between ALDHs with broad substrate specificities. A site on the World Wide Web has also been devoted to this alignment project.

Type
Research Article
Copyright
© 1999 The Protein Society

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