Acylpeptide hydrolase: inhibitors and some active site residues of the human enzyme.

A novel class of protease targets of phosphatidylethanolamine-binding proteins (PEBP): a study of the acylpeptide hydrolase and the PEBP inhibitor from the archaeon Sulfolobus solfataricus

“…However, as verified by gel filtration chromatography, the native enzyme had a molecular mass of 125 kDa and consisted of two identical subunits. Therefore the protein is likely to consist of a dimeric structure which is in contrast to the tetramer APEH mammalian counterpart 15,[17][18][19] but in agreement with the structural findings of the archaeal APEHs both from A. pernix 12 and P. horikoshii. 16 It is known that acyl-peptide hydrolase catalyzes the hydrolysis of N-terminally acetylated peptide to release N-acetyl amino acid.…”

“…9 So far, these enzymes have been found in a number of eukaryal 14,15 organisms and in some Archaea 12,16 but never in prokaryotes. Rat, 17 porcine, 18 human 19 and bovine 14,15 APEHs from different tissues, including blood, brain and liver, show significant sequence identity and are reported to form homotetramers. Moreover, APEH has been characterized from hyperthermophile Aeropyrum pernix K1, 12 whose crystal structure has also been resolved, 13 and from the thermophilic archaeon Pyrococcus horikoshii OT3.…”

“…Whilst human APEH is known to be deficient in small-cell lung and renal carcinomas, a role in the malignant state of these cell lines has not so far been established. [20][21][22] Furthermore, porcine brain APEH was found to be potently inhibited by organophosphorous compounds and it has been proposed as a new pharmacological target for the cognitive-enhancing effects of these compounds in the treatment of neurodegenerative diseases. 23 The aim of the present work was the isolation of the endogenous protease target of SsCEI, and the analysis of the protease/SsCEI interaction from a biochemical/structural point of view.…”

Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme

“…It is widely accepted that high ROS levels may have deleterious effects on macromolecules such as proteins and different proteolytic systems that operate in a number of different biochemical mechanisms aimed at tissue detoxification. In this context, recent studies assign to APEH (Acylaminoacyl Peptidase or acylamino-acid-releasing enzyme) a crucial role in these mechanisms, given its ability to process and degrade many protein substrates through both exo- and endopeptidase activity [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”

“…As such, it contains a peptidase domain with a α/β-hydrolase fold and an unusual β-propeller domain, which covers the catalytic triad [ 9 , 11 ]. From a physiological point of view, APEH plays a key role in protein metabolism by participating in amino acid recycling, as it catalyzes the hydrolysis of N-acetylated peptides/proteins yielding an N-acylated-amino acid and a peptide/protein with a free N-terminus [ 3 , 12 ]. Initially assumed to exclusively contribute to the protein turnover acting as exopeptidase, APEH was then demonstrated to have distinct functional properties to help organisms survive under adverse conditions, thus playing an important role in different biological processes.…”