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Relationships within the aldehyde dehydrogenase extended family
Author(s) -
Perozich John,
Nicholas Hugh,
Wang BiCheng,
Lindahl Ronald,
Hempel John
Publication year - 1999
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.8.1.137
Subject(s) - aldehyde dehydrogenase , nad+ kinase , biology , conserved sequence , biochemistry , cysteine , stereochemistry , active site , phylogenetic tree , peptide sequence , chemistry , enzyme , gene
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 102” 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.