Reaction: (1) cleavage of an N-acetyl or N-formyl amino acid from the N-terminus of a polypeptide
(2) internal cleavage of oxidized and glycated proteins
Other name(s): acylamino-acid-releasing enzyme; N-acylpeptide hydrolase; N-formylmethionine (fMet) aminopeptidase; α-N-acylpeptide hydrolase; oxidized protein hydrolase; acylpeptide hydrolase; AARE; AAP; OPH; AAH; APEH; ACPH
Comments: This is a bifunctional serine protease that has exopeptidase activity against Nα-acylated peptides and endopeptidase activity against oxidized and glycated proteins. In its exopeptidase mode the enzyme cleaves an N-acetyl or N-formyl amino acid from the N-terminus of a polypeptide. This class of enzymes is evolutionary deeply conserved and is found in bacteria, archaea, animals and plants with different quartenary structures. In humans, malfunction is linked to different types of cancer and sarcoma cell viability. In peptidase family S9 (prolyl oligopeptidase family).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, MEROPS, PDB, CAS registry number: 73562-30-8
References:
1. Tsunazawa, S., Narita, K. and Ogata, K. Acylamino acid-releasing enzyme from rat liver. J. Biochem. (Tokyo) 77 (1975) 89-102. [PMID: 1137989]
2. Fujino, T., Watanabe, K., Beppu, M., Kikugawa, K. and Yasuda, H. Identification of oxidized protein hydrolase of human erythrocytes as acylpeptide hydrolase. Biochim. Biophys Acta 1478 (2000) 102-112. [PMID: 10719179]
3. Yamauchi, Y., Ejiri, Y., Toyoda, Y. and Tanaka, K. Identification and biochemical characterization of plant acylamino acid-releasing enzyme. J. Biochem. 134 (2003) 251-257. [PMID: 12966075]
4. Bartlam, M., Wang, G., Yang, H., Gao, R., Zhao, X., Xie, G., Cao, S., Feng, Y. and Rao, Z. Crystal structure of an acylpeptide hydrolase/esterase from Aeropyrum pernix K1. Structure 12 (2004) 1481-1488. [PMID: 15296741]
5. Shimizu, K., Kiuchi, Y., Ando, K., Hayakawa, M. and Kikugawa, K. Coordination of oxidized protein hydrolase and the proteasome in the clearance of cytotoxic denatured proteins. Biochem Biophys Res Commun 324 (2004) 140-146. [PMID: 15464994]
6. Nakai, A., Yamauchi, Y., Sumi, S. and Tanaka, K. Role of acylamino acid-releasing enzyme/oxidized protein hydrolase in sustaining homeostasis of the cytoplasmic antioxidative system. Planta 236 (2012) 427-436. [PMID: 22398639]
7. Gogliettino, M., Cocca, E., Sandomenico, A., Gratino, L., Iaccarino, E., Calvanese, L., Rossi, M. and Palmieri, G. Selective inhibition of acylpeptide hydrolase in SAOS-2 osteosarcoma cells: is this enzyme a viable anticancer target. Mol. Biol. Rep. 48 (2021) 1505-1519. [PMID: 33471263]
8. Kiss-Szeman, A.J., Straner, P., Jakli, I., Hosogi, N., Harmat, V., Menyhard, D.K. and Perczel, A. Cryo-EM structure of acylpeptide hydrolase reveals substrate selection by multimerization and a multi-state serine-protease triad. Chem. Sci. 13 (2022) 7132-7142. [PMID: 35799812]