View source for 7qun


==CryoEM structure of mammalian AAP in complex with Meropenem==
<StructureSection load='7qun' size='340' side='right'caption='[[7qun]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qun]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa_domesticus Sus scrofa domesticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUN 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DWZ:(2S,3R,4S)-4-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-2-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-METHYL-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>DWZ</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=7qun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qun OCA], [https://pdbe.org/7qun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qun RCSB], [https://www.ebi.ac.uk/pdbsum/7qun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qun 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]
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== Publication Abstract from PubMed ==
The structure of porcine AAP (pAAP) in a covalently bound complex with meropenem was determined by cryo-EM to 2.1 A resolution, showing the mammalian serine-protease inhibited by a carbapenem antibiotic. AAP is a modulator of the ubiquitin-proteasome degradation system and the site of a drug-drug interaction between the widely used antipsychotic, valproate and carbapenems. The active form of pAAP - a toroidal tetramer - binds four meropenem molecules covalently linked to the catalytic Ser587 of the serine-protease triad, in an acyl-enzyme state. AAP is hindered from fully processing the antibiotic by the displacement and protonation of His707 of the catalytic triad. We show that AAP is made susceptible to the association by its unusually sheltered active pockets and flexible catalytic triads, while the carbapenems possess sufficiently small substituents on their beta-lactam rings to fit into the shallow substrate-specificity pocket of the enzyme.

A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase-meropenem complex.,Kiss-Szeman AJ, Takacs L, Orgovan Z, Straner P, Jakli I, Schlosser G, Masiulis S, Harmat V, Menyhard DK, Perczel A Chem Sci. 2022 Nov 8;13(48):14264-14276. doi: 10.1039/d2sc05520a. eCollection , 2022 Dec 14. PMID:36545146<ref>PMID:36545146</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7qun" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa domesticus]]
[[Category: Harmat V]]
[[Category: Jakli I]]
[[Category: Kiss-Szeman AJ]]
[[Category: Masiulis S]]
[[Category: Menyhard KD]]
[[Category: Perczel A]]
[[Category: Straner P]]