An algorithm for detecting amino acid residues characteristic of individual protein families from within aligned collections of paralogous sequences, and its application to the ALDH3 family versus the rest of the ALDH extended family is described. Residues illuminated by this analysis include a key intramolecular tether, a lysine that makes an intersubunit contact at the dimer interface, three residues in close association with the substrate-binding funnel, and a pair of residues suggested to participate in proton relay during the catalytic cycle.
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