A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex

Kiss-Szemán, Anna; Takács, Luca; Orgován, Zoltán; Stráner, Pál; Jákli, Imre; Schlosser, Gitta; Masiulis, Simonas; Harmat, Veronika; Menyhárd, Dóra K.; Perczel, András

doi:10.1039/d2sc05520a

Cited by 2 publications

(1 citation statement)

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“…MEPM was reported to interact with VPA, with one of the mechanisms as the inhibition of β‐glucuronidase. A previous study indicated that VPA‐glucuronidase (VPA‐G) could be hydrolyzed back to VPA by acylpeptide hydrolase (APEH) [ 6 ], and the activity of APEH was reversibly and irreversibly suppressed by MEPM [ 7 ]. A decrease in activity of APEH by MEPM may cause increased urinary excretion of VPA‐G with concomitant reduction in plasma VPA concentration [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid

Gu,

Zhang,

Yuan

et al. 2024

Clinical Laboratory Analysis

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ObjectiveThis study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co‐administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA.MethodsWe retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co‐administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co‐administerd VPA and other broad‐spectrum antibiotics were allocated to the control group.ResultsThe exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co‐administration (24.6 ± 4.3 μg/mL) compared with that before co‐administration (88.8 ± 13.6 μg/mL, p < 0.0001), and it was partly recovered with the termination of co‐administration (39.8 ± 13.2 μg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before‐during and before‐after (p = 0.074 and 0.153, respectively). Seizure duration during VPA–MEPM co‐administration was not significantly different from that before co‐administration (p = 0.291).ConclusionsIn this study, the reduced plasma concentration of VPA induced by the co‐administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted.Trial RegistrationChinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020

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Section: Introductionmentioning

confidence: 99%

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid

Gu,

Zhang,

Yuan

et al. 2024

Clinical Laboratory Analysis

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Quantum chemical package Jaguar: A survey of recent developments and unique features

Cao,

Balduf,

Beachy

et al. 2024

The Journal of Chemical Physics

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This paper is dedicated to the quantum chemical package Jaguar, which is commercial software developed and distributed by Schrödinger, Inc. We discuss Jaguar’s scientific features that are relevant to chemical research as well as describe those aspects of the program that are pertinent to the user interface, the organization of the computer code, and its maintenance and testing. Among the scientific topics that feature prominently in this paper are the quantum chemical methods grounded in the pseudospectral approach. A number of multistep workflows dependent on Jaguar are covered: prediction of protonation equilibria in aqueous solutions (particularly calculations of tautomeric stability and pKa), reactivity predictions based on automated transition state search, assembly of Boltzmann-averaged spectra such as vibrational and electronic circular dichroism, as well as nuclear magnetic resonance. Discussed also are quantum chemical calculations that are oriented toward materials science applications, in particular, prediction of properties of optoelectronic materials and organic semiconductors, and molecular catalyst design. The topic of treatment of conformations inevitably comes up in real world research projects and is considered as part of all the workflows mentioned above. In addition, we examine the role of machine learning methods in quantum chemical calculations performed by Jaguar, from auxiliary functions that return the approximate calculation runtime in a user interface, to prediction of actual molecular properties. The current work is second in a series of reviews of Jaguar, the first having been published more than ten years ago. Thus, this paper serves as a rare milestone on the path that is being traversed by Jaguar’s development in more than thirty years of its existence.

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A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex

Abstract: The structure of porcine AAP (pAAP) in a covalently bound complex with meropenem was determined by cryo-EM to 2.1 Å resolution, showing the mammalian serine-protease inhibited by a carbapenem antibiotic....

Cited by 2 publications

References 72 publications

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid

Quantum chemical package Jaguar: A survey of recent developments and unique features

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