Article
Biochemistry & Molecular Biology
Beata Lemli, Zuzana Lomozova, Tamas Huber, Andras Lukacs, Miklos Poor
Summary: This study investigates the effects of different Heme site ligands on the interaction between warfarin and Human serum albumin (HSA). The results show that these ligands can significantly modulate the binding affinity of warfarin to HSA, and the outcome can even be concentration dependent. The fluorescence spectroscopic results may be misleading in these ligand-albumin interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Casey Trimmer, Randy Arroyave, Christine Vuilleumier, Lily Wu, Aleksey Dumer, Christie DeLaura, Jehoon Kim, Georgia M. Pierce, Maria Borisovska, Florian De Nanteuil, Matthew Emberger, Yakov Varganov, Christian Margot, Matthew E. Rogers, Patrick Pfister
Summary: Odor perception is determined by the detection of environmental volatiles at the periphery of the olfactory system. Combinatorial activation of odorant receptors allows discrimination of numerous odorants, and recent studies indicate inhibitory modulation of receptor activity in the presence of odorant mixtures. Human OR5AN1 plays a role in musk detection and certain odorants act as positive allosteric modulators, enhancing its activity in binary mixtures. This allosteric modulation of odorant receptors is perceptually relevant and adds complexity to odor coding in the peripheral olfactory system.
Article
Chemistry, Analytical
Martin Mathay, Andrew Keller, James E. Bruce
Summary: Recently, mass spectrometry methods have been used to quantitatively study protein-ligand interactions by assessing protein structural stability. Different protein-denaturation approaches, such as TPP and SPROX, have their own advantages and challenges. A new method combining protein-denaturation principles with quantitative cross-linking mass spectrometry has been developed, allowing the evaluation of ligand-induced protein engagement. This method has been successfully applied to identify ligand-stabilized cross-linked lysine pairs in bovine serum albumin and ligand bilirubin.
ANALYTICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Marjorie Damian, Maxime Louet, Antoniel Augusto Severo Gomes, Celine M'Kadmi, Severine Denoyelle, Sonia Cantel, Sophie Mary, Paulo M. Bisch, Jean-Alain Fehrentz, Laurent J. Catoire, Nicolas Floquet, Jean-Louis Baneres
Summary: The membrane plays a crucial role in modulating the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific lipid interactions and bulk effects. PIP2 and GM3 induce shifts in the conformational equilibrium of GHSR, favoring G protein activation in different ways.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Hebatalla Mohamed, Amna Ghith, Stephen G. Bell
Summary: The cytochrome P450 superfamily of enzymes can catalyse oxidation reactions and their heme and active site environment can be studied using UV-visible absorbance spectroscopy. The binding of imidazole and pyridine-based ligands to different forms of bacterial cytochrome P450 enzymes was evaluated using this technique. The majority of ligands interacted with the heme as expected, but differences in heme environment were observed across enzyme/ligand combinations.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Chang-Run Guo, Zhong-Zhe Zhang, Xing Zhou, Meng-Yang Sun, Tian-Tian Li, Yun-Tao Lei, Yu-Hao Gao, Qing-Quan Li, Chen-Xi Yue, Yu Gao, Yi-Yu Lin, Cui-Yun Hao, Chang-Zhu Li, Peng Cao, Michael X. Zhu, Ming-Qiang Rong, Wen-Hui Wang, Ye Yu
Summary: The study demonstrates a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and shows that quercetin and PSFL2915 can achieve antitussive effects by preventing allosteric changes of IP-HD in P2X3.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Werner Treptow
Summary: Membrane proteins can respond to various ligands under external stimuli, including small low-affinity molecules. Understanding the modulation of protein function by such ligands is challenging due to their multiple degenerate interactions with the protein. A new theoretical model based on the Boltzmann model is proposed, which allows the description of the equilibrium shifts of the protein in the presence of small low-affinity ligands. This model can be compared to experimental data at the atomic level, making it useful for interpreting protein-ligand interactions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Werner Treptow
Summary: Membrane proteins respond to a variety of ligands, including small low-affinity molecules, under an external stimulus. Characterizing the atomic-level interactions between these ligands and membrane proteins at dilute concentrations is challenging. A new theoretical description based on the two-state Boltzmann model is developed to understand the allosteric modulation of membrane proteins in the presence of small low-affinity ligands and external stimuli. This model allows for the interpretation of experimental data at the atomic level.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Dipak Kumar Sahoo, Souradip Dasgupta, Tanuja Kistwal, Anindya Datta
Summary: This paper investigates the binding interactions between Human serum albumin (HSA) and Znsalampy using fluorescence spectroscopic techniques. The binding constant is estimated from the quenching of HSA's single Trp residue by Znsalampy. Fluorescence correlation spectroscopy (FCS) is used to monitor the protein-ligand binding. The location of Znsalampy in its complex with HSA is determined through competitive binding experiments and molecular docking calculations. The Znsalampy-HSA interaction falls within the ideal range for biological applications and Znsalampy is found to be in proximity to Sudlow's site I. The esterase activity of HSA is unaffected in the presence of Znsalampy. Thus, Znsalampy may be a potential probe and biomarker in biomedical applications.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Spencer Cholak, James W. Saville, Xing Zhu, Alison M. Berezuk, Katharine S. Tuttle, Omid Haji-Ghassemi, Francisco J. Alvarado, Filip Van Petegem, Sriram Subramaniam
Summary: The release of Ca2+ from the sarcoplasmic reticulum (SR), facilitated by ryanodine receptors (RyRs), is crucial for excitation-contraction coupling. In this study, cryo-EM structures of RyR1 bound to various ATP derivatives were determined, revealing that AMP is the smallest derivative capable of inducing structural rearrangements associated with channel activation. Additionally, cAMP was found to induce similar structural changes and increase channel opening, suggesting its potential role as an endogenous modulator of RyR1 conductance.
Article
Biology
Julian Alexander Schreiber, Anastasia Derksen, Gunnar Goerges, Sven Schuette, Jasmin Soergel, Aytug K. Kiper, Nathalie Strutz-Seebohm, Tobias Ruck, Sven G. Meuth, Niels Decher, Guiscard Seebohm
Summary: It is reported that the drug cloxyquin activates the TWIK-related spinal cord K+ channel (TRESK) by stabilizing the inner selectivity filter. This finding has significant implications for future drug development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemical Research Methods
Sazia Iftekhar, Zhao Li, Pingyang Tao, Saumen Poddar, David S. Hage
Summary: Ultrafast affinity extraction and affinity microcolumns were used to evaluate the effect of advanced stage glycation on HSA and its binding to warfarin. The results showed that MGO-modified HSA had higher association equilibrium constants with warfarin compared to normal HSA, while GO-modified HSA had similar values.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Giovanna De Simone, Alessandra di Masi, Paolo Ascenzi
Summary: Human serum albumin (HSA) plays various important roles in the body, such as maintaining oncotic pressure, carrying fatty acids, recognizing metal ions, and affecting drug metabolism. It also exhibits antioxidant properties and is critical for detoxification and pro-drug activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Ravi Jasuja, Daniel Spencer, Abhilash Jayaraj, Liming Peng, Meenakshi Krishna, Brian Lawney, Priyank Patel, Bhyravabhotla Jayaram, Kelly M. Thayer, David L. Beveridge, Shalender Bhasin
Summary: It has been discovered that the binding of estradiol to SHBG is nonlinear and depends on the concentrations of estradiol and SHBG. After estradiol binds to each SHBG monomer, it will differentially change the conformational and energy landscapes of both monomers.
Article
Medical Laboratory Technology
Hiromi Uekita, Hiroyasu Yamamoto, Ryu Niinaga, Noriko Yamane, Manami Yoshii, Keiko Yamauchi-Takihara, Shinji Kihara
Summary: The study found a correlation between serum Mac-2BP concentrations and clinical parameters related to metabolic syndrome, but the significance was not evident in multivariate analysis. IFN-gamma stimulation led to increased Mac-2BP and decreased ABCA1 and apo A-I mRNA concentrations in HepG2 cells.
CLINICA CHIMICA ACTA
(2021)
Article
Biochemistry & Molecular Biology
Sara Garcia-Vinuales, Michele F. M. Sciacca, Valeria Lanza, Anna Maria Santoro, Giulia Grasso, Grazia R. Tundo, Diego Sbardella, Massimiliano Coletta, Giuseppe Grasso, Carmelo La Rosa, Danilo Milardi
Summary: Alzheimer's Disease (AD) is characterized by amyloid deposits in the brain, with factors such as genetic background, other diseases, and lifestyle contributing to its development. Recent studies suggest a link between impaired lipid metabolism and A beta deposition, with membrane-bound A beta assemblies playing a key role in neurotoxicity. Additionally, dysregulation of lipid levels and toxic A beta aggregation may be linked to derangements in cellular pathways such as ubiquitin proteasome and autophagy. Understanding the role of lipids in A beta aggregation and proteostasis could lead to valuable treatment options.
CHEMISTRY AND PHYSICS OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Giovanna De Simone, Alessandra di Masi, Alessandra Pesce, Martino Bolognesi, Chiara Ciaccio, Lorenzo Tognaccini, Giulietta Smulevich, Stefania Abbruzzetti, Cristiano Viappiani, Stefano Bruno, Sara Della Monaca, Donatella Pietraforte, Paola Fattibene, Massimo Coletta, Paolo Ascenzi
Summary: The structural and functional properties of nitrobindins in ferrous Mycobacterium tuberculosis (Mt-Nb) and human (Hs-Nb) were investigated, revealing significant differences in ligand binding and reaction rates compared to most hemoproteins. The lack of pH dependence in the coordination process and the weakening or cleavage of the proximal Fe-His bond upon ligand binding were highlighted as distinctive features of these nitrobindins. This suggests a unique functional role for Nbs distinct from other eukaryotic and prokaryotic hemoproteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Spectroscopy
Federico Sebastiani, Lisa Milazzo, Cecile Exertier, Maurizio Becucci, Giulietta Smulevich
Summary: In heme proteins, two different heme orientations can exist, and the reversal of heme orientation may alter the functional properties of the protein. Resonance Raman spectroscopy provides detailed information on the structure of reversed heme, offering insights into the effects of heme rotation on peripheral substituents. It is proposed that resonance Raman spectroscopy can be a sensitive tool for detecting heme orientational disorder in heme proteins without structural data.
JOURNAL OF RAMAN SPECTROSCOPY
(2021)
Article
Chemistry, Multidisciplinary
Eleonora Roschi, Cristina Gellini, Marilena Ricci, Santiago Sanchez-Cortes, Claudia Focardi, Bruno Neri, Juan Carlos Otero, Isabel Lopez-Tocon, Giulietta Smulevich, Maurizio Becucci
Summary: Silver nanoparticles functionalized with CD-SH were used for detecting bisphenols A, B, and S through SERS, with an improved sensitivity. Theoretical DFT calculations allowed for structural analysis of the CD-SH/BP complex, confirming an external interaction between hydroxyl groups of BPs and CD. Experimental evidence and testing supported the lack of actual inclusion of BPs inside the CD cavity. The SERS sensor and data analysis procedures were validated for detecting BPs in milk extracts.
Review
Chemistry, Medicinal
Francesco Oddone, Luca Rossetti, Mariacristina Parravano, Diego Sbardella, Massimo Coletta, Lucia Ziccardi, Gloria Roberti, Carmela Carnevale, Dario Romano, Gianluca Manni, Vincenzo Parisi
Summary: Cytidine 5'-diphosphocholine has been extensively studied in systemic neurodegenerative diseases, while its use in ophthalmological neurodegenerative diseases is based on its multifactorial mechanism of action and involvement in multiple metabolic pathways, including intracellular proteostasis.
Article
Biochemistry & Molecular Biology
Diego Sbardella, Grazia Raffaella Tundo, Massimo Coletta, Gianluca Manni, Francesco Oddone
Summary: Steroid-induced glaucoma is a severe eye condition characterized by rapidly increasing intraocular pressure due to metabolic dysregulation of Trabecular Meshwork Cells. Exposure to steroids inhibits the autophagy process in TMCs, possibly through the Ubiquitin Proteasome System.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Correction
Multidisciplinary Sciences
Diego Sbardella, Grazia Raffaella Tundo, Luisa Campagnolo, Giuseppe Valacchi, Augusto Orlandi, Paolo Curatolo, Giovanna Borsellino, Maurizio D'Esposito, Chiara Ciaccio, Silvia Di Cesare, Donato Di Pierro, Cinzia Galasso, Marta Elena Santarone, Joussef Hayek, Massimiliano Coletta, Stefano Marini
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Thomas Gabler, Federico Sebastiani, Johannes Helm, Andrea Dali, Christian Obinger, Paul G. Furtmueller, Giulietta Smulevich, Stefan Hofbauer
Summary: Coproporphyrin III serves as the substrate for coproporphyrin ferrochelatases (CpfCs), playing a crucial role in the coproporphyrin-dependent haeme biosynthesis pathway utilized mainly by monoderm bacteria. This pathway differs from the protoporphyrin-dependent pathway, commonly used by diderm bacteria, showcasing distinct substrate ferrochelatases.
Article
Multidisciplinary Sciences
Monica Benvenuto, Sara Ciuffa, Chiara Focaccetti, Diego Sbardella, Sara Fazi, Manuel Scimeca, Grazia Raffaella Tundo, Giovanni Barillari, Maria Segni, Elena Bonannol, Vittorio Manzari, Andrea Modesti, Laura Masuelli, Massimo Coletta, Roberto Bei
Summary: Bortezomib shows anti-tumor activity in head and neck cancer cell lines, delaying tumor growth and prolonging survival in transgenic mice, while adjusting the tumor microenvironment through increasing immune cell infiltration and decreasing vessel density.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Grazia R. Tundo, Diego Sbardella, Francesco Oddone, Anna A. Kudriaeva, Pedro M. Lacal, Alexey A. Belogurov, Grazia Graziani, Stefano Marini
Summary: The immunoproteasome plays a crucial role in antigen presentation and its modulation presents promising research opportunities. Immunotherapy has shown significant advancements, however, a broader understanding of cancer cell antigen processing dynamics is still required for further improvements.
Article
Spectroscopy
Federico Sebastiani, Chiara Niccoli, Hanna Michlits, Riccardo Risorti, Maurizio Becucci, Stefan Hofbauer, Giulietta Smulevich
Summary: The actinobacterial coproheme decarboxylase catalyzes the final reaction to generate heme b in the presence of hydrogen peroxide. Excess hydrogen peroxide causes hydroxylation of ring C or D, leading to the formation of an iron chlorin-type heme d species.
JOURNAL OF RAMAN SPECTROSCOPY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Dali, Thomas Gabler, Federico Sebastiani, Alina Destinger, Paul Georg Furtmueller, Vera Pfanzagl, Maurizio Becucci, Giulietta Smulevich, Stefan Hofbauer
Summary: Coproporphyrin ferrochelatases (CpfCs) are enzymes that catalyze the penultimate step in the coproporphyrin-dependent heme biosynthesis pathway. The discovery of the correct substrate for these ferrochelatases and the characterization of their binding mode provide valuable insights into the iron insertion process. This knowledge is essential for understanding the preconditions and mechanisms of iron insertion in CpfCs.
Article
Biochemistry & Molecular Biology
Federico Sebastiani, Chiara Baroni, Gaurav Patil, Andrea Dali, Maurizio Becucci, Stefan Hofbauer, Giulietta Smulevich
Summary: Monoderm bacteria accumulate heme b through the coproporphyrin-dependent biosynthesis pathway. The decarboxylation of propionate groups in coproheme by coproheme decarboxylase (ChdC) is a stepwise process. H-bond interactions in the pocket of ChdCs play a crucial role in stabilizing the active site and enzyme functionality, which were evaluated through characterization of mutants complexed with coproheme and heme b via spectroscopies.
Article
Biochemistry & Molecular Biology
Thomas Gabler, Andrea Dali, Federico Sebastiani, Paul Georg Furtmueller, Maurizio Becucci, Stefan Hofbauer, Giulietta Smulevich
Summary: Understanding the reaction mechanism of enzymes is challenging, but studying model substrates can provide valuable information. In this study, we investigated the mechanism of ferrous iron incorporation in a bacterial enzyme complex and discovered the role of hydrogen bond interactions in this process.