9S6B
Aeropyrum pernix acylaminoacyl peptidase co-crystallized with meropenem.
Summary for 9S6B
| Entry DOI | 10.2210/pdb9s6b/pdb |
| Related | 3O4H |
| Descriptor | Acylamino-acid-releasing enzyme, (2R,2'R)-3,3'-oxydipropane-1,2-diol (3 entities in total) |
| Functional Keywords | serine protease, hbpg, ligand binding, hydrolase |
| Biological source | Aeropyrum pernix K1 |
| Total number of polymer chains | 4 |
| Total formula weight | 252756.69 |
| Authors | Harmat, V.,Takacs, L.,Kiss-Szeman, A.,Banoczi, Z.,Jakli, I.,Hosogi, N.,Traore, D.A.K.,Perczel, A.,Menyhard, D.K. (deposition date: 2025-07-31, 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 | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
Download full validation report
