View source for 9hxq


==Cryo-EM structure of acylaminoacyl peptidase (AAP) in covalent complex with inhibitor AEBSF==
<StructureSection load='9hxq' size='340' side='right'caption='[[9hxq]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hxq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HXQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AES:4-(2-AMINOETHYL)BENZENESULFONYL+FLUORIDE'>AES</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9hxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hxq OCA], [https://pdbe.org/9hxq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hxq RCSB], [https://www.ebi.ac.uk/pdbsum/9hxq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hxq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACPH_PIG ACPH_PIG] This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus (By similarity). It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser (By similarity). Also, involved in the degradation of oxidized and glycated proteins (By similarity).[UniProtKB:P13676][UniProtKB:P13798]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 alpha/beta hydrolases sharing essentially the same fold.

Ligand binding Pro-miscuity of acylpeptide hydrolase, structural analysis of a detoxifying serine hydrolase.,Kiss-Szeman AJ, Takacs L, Jakli I, Banoczi Z, Hosogi N, Traore DAK, Harmat V, Perczel A, Menyhard DK Protein Sci. 2025 Nov;34(11):e70320. doi: 10.1002/pro.70320. PMID:41074793<ref>PMID:41074793</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hxq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Harmat V]]
[[Category: Kiss-Szeman AJ]]
[[Category: Menyhard DK]]
[[Category: Perczel A]]