A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex
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Tartalom: http://real.mtak.hu/162380/
Archívum: REAL
Gyűjtemény: Status = Published
Subject = Q Science / természettudomány: QD Chemistry / kémia: QD05 Crystallography / kristálytan
Subject = Q Science / természettudomány: QD Chemistry / kémia
Subject = Q Science / természettudomány: QD Chemistry / kémia: QD04 Organic chemistry / szerves kémia
Type = Article
Cím:
A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex
Létrehozó:
Kiss-Szemán, Anna
Takács, Luca
Orgován, Zoltán
Stráner, Pál
Jákli, Imre
Schlosser, Gitta
Masiulis, Simonas
Harmat, Veronika
K. Menyhárd, Dóra
Perczel, András
Kiadó:
Royal Society of Chemistry
Dátum:
2022
Téma:
QD Chemistry / kémia
QD04 Organic chemistry / szerves kémia
QD05 Crystallography / kristálytan
Tartalmi leírás:
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 b-lactam rings to fit into the shallow substrate-specificity pocket of the enzyme.
Nyelv:
angol
Típus:
Article
PeerReviewed
info:eu-repo/semantics/article
Formátum:
text
Azonosító:
Kiss-Szemán, Anna and Takács, Luca and Orgován, Zoltán and Stráner, Pál and Jákli, Imre and Schlosser, Gitta and Masiulis, Simonas and Harmat, Veronika and K. Menyhárd, Dóra and Perczel, András (2022) A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex. Chemical Science, 13. p. 14264. ISSN 2041-6520
Kapcsolat:
doi: 10.1039/d2sc05520a