29. Electrostatics of Covalent Inhibition During Antibiotic Resistance
The widespread design of covalent drugs has focused on crafting reactive groups of proper electrophilicity and positioning. We found that environmental electric fields projected onto a reactive chemical bond, an overlooked design element, play essential roles in the covalent inhibition of TEM-1 β-lactamase by avibactam.
Zhi et al., J. Am. Chem. Soc., 2022
Protein Electric Fields Enable Faster and Longer-Lasting Covalent Inhibition of β-Lactamases.
DOI: 10.1021/jacs.2c09876
25. Proton-Pumping Microbial Rhodopsin from pathogenic fungi
Microbial rhodopsins have recently been discovered in pathogenic fungi and have been postulated to be involved in signaling during the course of an infection. Here, we characterize the photocycle of Ustilago maydis Rhodopsin 1.
La Greca & Chen et al., Front. Mol. Biosci., 2022, 9, 826990
The Photoreaction of the Proton-Pumping Rhodopsin 1 From the Maize Pathogenic Basidiomycete Ustilago maydis
DOI: 10.3389/fmolb.2022.826990
24. Antibiotic Resistance trough Electrostatics and Chemical Positioning
What are the physical origins of antibiotic resistance? Using experiments and theory we explore the active site electric fields and chemical positioning in β-lactamases.
Schneider & Kozuch et al., ACS Centr. Sci., 2021, 7, 1996-2008
The Interplay of Electrostatics and Chemical Positioning in the Evolution of Antibiotic Resistance in TEM β-Lactamases.
DOI: 10.1021/acscentsci.1c00880
20. Site-specific 13C-labeling of β-Lactam Drugs
In order to perform our study (24) on the evolution of electric fields in β-lactamases, we need site-specifically 13C-labeled penicillin G and cefotaxime. To our surprise there are no commercial sources, so we did it ourselves.
Kozuch et al., ACS Chem. Bio., 2020, 15, 1148-1153
Biosynthetic incorporation of site-specific isotopes in β-lactam antibiotics enables biophysical studies.
DOI: 10.1021/acschembio.9b01054
18. Cathelicidine LL-37 – A Peptide Of Our Innate Antimicrobial Immune System
Cathelicidins are a family of host defense antimicrobial peptides in mammalian species. Among them, LL-37 is the only peptide of this family found in humans. We combine microbiology, spectroscopy and simulations to unravel its mode of action.
de Miguel Catalina & Forbrig et al., Biochemistry, 2019
The C-Terminal VPRTES Tail of LL-37 Influences the Mode of Attachment to a Lipid Bilayer and Antimicrobial Activity.
DOI: 10.1021/acs.biochem.8b01297
17. On the pH-modulated Ru-based pro-drug activation mechanism
Ru-based anticancer drugs can be administered as the inactive RuIII-prodrug Aziru and then activated via a redox transition to RuII. This transition is pH dependent shifting the redox potential of the RuII/RuIII couple by >600 mV.
Caterino et al., Inorg. Chem., 2018
On the pH-modulated Ru-based pro-drug activation mechanism.
DOI: 10.1021/acs.inorgchem.8b02667
12. Monitoring how Transmembrane Electrostatics reorient a-helices in Membranes
Antimicrobial peptides are the first line of defense after contact of an infectious invader, often acting via interactions with the target membrane. The transmembrane electrostatics can play a major governing role in antimicrobial action. We show, for the first time using SEIRAS, that we can control the large-scale reorientation of AMP helices to form the active ion channel form.
Forbrig et al., Langmuir, 2018
Monitoring the orientational changes of alamethicin during incorporation in bilayer lipid membranes.
DOI: 10.1021/acs.langmuir.7b04265
6. The mitochondrial human voltage-dependent anion channel (HVDAC) acts via deformation Its b-barrel structure
The voltage-dependent anion channel (VDAC) regulates the transfer of metabolites between the cytosol and the mitochondrium. Opening and partial closing of the channel is known to be driven by the transmembrane potentia. Our results indicate alterations of the inclination angle of the β-strands as crucial molecular events, reflecting an expansion or contraction of the β-barrel pore.
Kozuch et al., Phys. Chem. Chem. Phys., 2014
Voltage-dependent structural changes of the membrane-bound anion channel hVDAC1 probed by SEIRA and electrochemical impedance spectroscopy.
DOI: 10.1039/C4CP00167B
Kozuch Lab 