Thiol proteases and aldehyde dehydrogenases: evolution from a common thiolesterase precursor?
The C-terminal 222 residues of human liver aldehyde dehydrogenase can be aligned with the C-terminal 226 residues of a thiol protease from Dictyostelium discoideum to yield 47 residue identities, including matching active site cysteine residues. A multiple alignment with three more aldehyde dehydrogenases and three more thiol proteases yields three regions with clustered residue similarities. In the tertiary structure of papain, these three regions are in close proximity although widely separated in primary structure, and many conserved residues are located in the active site groove. The three-dimensional relationships, the common thiol ester mechanisms of the enzymes, the locations of exon boundaries in the dehydrogenase and protease genes, and the conservation of internal salt-bridging and disulfide-paired residues in papain, all appear compatible with the hypothesis of an ancestral relationship between thiol proteases and aldehyde dehydrogenases.
Hempel
J
J
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Nicholas
H
H
Jörnvall
H
H
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000595:Amino Acid Sequence; D005075:Biological Evolution; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005091:Exons; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010206:Papain / Q000235:genetics; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid
D000444:Aldehyde Dehydrogenase; D003546:Cysteine Endopeptidases; D010206:Papain