Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities.
An 87% identity has been found between the reported cDNA sequence that encodes acylpeptide hydrolase (EC 3.4.19.1) [Mitta, M., Asada, K., Uchimura, Y., Kimizuka, F., Kato, I., Sakiyama, F. & Tsunasawa, S. (1989) J. Biochem. 106, 548-551] and a cDNA transcribed from a locus (DNF15S2) on the short arm of human chromosome 3, reported by Naylor et al. [Naylor, S.L., Marshall, A., Hensel, C., Martinez, P.F., Holley, B. & Sakaguchi, A.Y. (1989) Genomics 4, 355-361]; the DNF15S2 locus suffers deletions in small cell lung carcinoma associated with a reduction or loss of acylase activity (EC 3.5.1.14). Acylpeptide hydrolase catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetylamino acid formed by acylpeptide hydrolase is further processed to acetate and a free amino acid by an acylase. The substrates for the acylpeptide hydrolase and the acylase behave in a reciprocal manner since acylpeptide hydrolase binds but does not process acetylamino acids and the acylase binds acetylpeptides but does not hydrolyze them; however, the two enzymes share the same specificity for the acyl group. These findings indicate some common functional features in the protein structures of these two enzymes. Since the gene coding for acylpeptide hydrolase is within the same region of human chromosome 3 (3p21) that codes for the acylase and deletions at this locus are also associated with a decrease in acylase activity, there is a close genetic relationship between the two enzymes. There could also be a relationship between the expression of these two enzymes and acetylated peptide growth factors in some carcinomas.
Jones
W M
WM
Rockefeller University, New York, NY 10021.
Scaloni
A
A
Bossa
F
F
Popowicz
A M
AM
Schneewind
O
O
Manning
J M
JM
D000409:Alanine; D000581:Amidohydrolases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002893:Chromosomes, Human, Pair 3; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity
D009842:Oligopeptides; D010447:Peptide Hydrolases; D000626:Aminopeptidases; C038220:acylaminoacyl-peptidase; D000581:Amidohydrolases; C019665:amidase; D000409:Alanine