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Thiol proteases and aldehyde dehydrogenases: Evolution from a common thiolesterase precursor?
Author(s) -
Hempel John,
Nicholas Hugh,
Jörnvall Hans
Publication year - 1991
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340110303
Subject(s) - proteases , papain , biochemistry , cysteine , thiol , aldehyde , active site , aldehyde dehydrogenase , residue (chemistry) , chemistry , protease , enzyme , stereochemistry , biology , catalysis
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.