9HXQ
Cryo-EM structure of acylaminoacyl peptidase (AAP) in covalent complex with inhibitor AEBSF
Summary for 9HXQ
| Entry DOI | 10.2210/pdb9hxq/pdb |
| Related | 7px8 7qun 9gne 9gou |
| EMDB information | 52489 |
| Descriptor | Acylamino-acid-releasing enzyme, 4-(2-AMINOETHYL)BENZENESULFONYL FLUORIDE (2 entities in total) |
| Functional Keywords | inhibitor, covalent, serine-protease, acylpeptide hydrolase, apeh, oph, acylaminoacyl peptidase, sulphonate, hydrolase |
| Biological source | Sus scrofa (pig) |
| Total number of polymer chains | 4 |
| Total formula weight | 326110.50 |
| Authors | Kiss-Szeman, A.J.,Menyhard, D.K.,Harmat, V.,Perczel, A. (deposition date: 2025-01-08, release date: 2025-10-22) |
| Primary citation | Kiss-Szeman, A.J.,Takacs, L.,Jakli, I.,Banoczi, Z.,Hosogi, N.,Traore, D.A.K.,Harmat, V.,Perczel, A.,Menyhard, D.K. Ligand binding Pro-miscuity of acylpeptide hydrolase, structural analysis of a detoxifying serine hydrolase. Protein Sci., 34:e70320-e70320, 2025 Cited by PubMed Abstract: Acylpeptide hydrolase (APEH) or acylaminoacyl-peptidase (AAP) is a serine hydrolase that regulates protein metabolism. It can also bind to and process unusual substrates, acting as a detoxifier. To better understand its promiscuous specificity, we determined the cryo-EM structures of mammalian APEH complexed with classical serine protease partners: a chloromethyl-ketone (CMK) inhibitor, an organophosphate (OP) pesticide (dichlorvos), and benzenesulfonyl-fluoride. Since CMK derivatives of N-acetylated peptides were suggested to induce apoptosis by inhibiting APEH, while OP complexes may serve as biomarkers of OP exposure and are linked to cognitive enhancement, these complexes carry physiological significance. We identified a unique strand-breaker Pro residue in the hydrolase domain, which relaxes the active site into a partially inactivated but more spacious conformation, transforming the classical serine protease apparatus into a versatile yet potent hydrolysis center with broad specificity, distinguishing the mammalian enzyme not only from other APEHs but also from serine α/β hydrolases sharing essentially the same fold. PubMed: 41074793DOI: 10.1002/pro.70320 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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