Article
Biology
Sophia Manukian, Gerrick E. Lindberg, Emily Punch, Sudarshi Premawardhana Dassanayake Mudiyanselage, Matthew J. Gage
Summary: The importance of pH shifts in biological systems is often overlooked. This study investigates the impact of non-ionizable residues on the pH sensitivity of the poly-E motif of muscle protein titin. The results highlight the influence of aromatic amino acids and proline residues on the conformational flexibility of this region.
Article
Biology
Bixia Zhang, ChulHee Kang, Dmitri R. Davydov
Summary: This study investigates the conformational transitions of SbCPR using rapid scanning stop-flow and pressure-perturbation spectroscopy. The results reveal that, although the closed conformation predominates, the population of the open state significantly increases upon the formation of the disemiquinone state. This research not only elucidates the functional choreography of plant CPRs but also demonstrates the high exploratory potential of a combination of pressure-perturbation approach with FRET-based monitoring of protein conformational transitions.
Article
Chemistry, Multidisciplinary
Hanquan Su, Joshua M. Brockman, Yuxin Duan, Navoneel Sen, Hemani Chhabra, Alisina Bazrafshan, Aaron T. Blanchard, Travis Meyer, Brooke Andrews, Jonathan P. K. Doye, Yonggang Ke, R. Brian Dyer, Khalid Salaita
Summary: The origami polymer force clamp (OPFC) is a technology that enables parallel operations to be conducted in single-molecule force spectroscopy (SMFS) to address the issue of serial and slow measurements. It allows for the manipulation of multiple molecules under force simultaneously without the need for dedicated instruments or surface tethering.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Genetics & Heredity
Xiangyan Shi, Ziwei Zhai, Yinglu Chen, Jindi Li, Lars Nordenskiold
Summary: This review summarizes recent advances in the study of chromatin dynamics and their regulatory factors, focusing on the conformational and dynamic properties of nucleosomes and nucleosome-protein complexes, and their implications for functional response and relevance.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Shuheng Huang, Hu Mei, Laichun Lu, Zuyin Kuang, Yu Heng, Lei Xu, Xiaoqi Liang, Minyao Qiu, Xianchao Pan
Summary: Caspase-6 is a key molecular target for neurodegeneration treatment, undergoing distinct conformational transitions upon substrate binding.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Richard J. Lindsay, Rachael A. Mansbach, S. Gnanakaran, Tongye Shen
Summary: The conformational ensemble of intrinsically disordered proteins, such as α-synuclein, is crucial for understanding and preventing pathologies. Under low pH conditions, neutralization of negatively charged residues leads to compaction of the C-terminal portion of α-synuclein, while internal reorganization allows it to maintain its overall end-to-end distance.
BIOPHYSICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hannah Maus, Stefan J. Hammerschmidt, Gerald Hinze, Fabian Barthels, Victor H. Perez Carrillo, Ute A. Hellmich, Thomas Basche, Tanja Schirmeister
Summary: By using a combination of methods including smFRET, thermal shift assays, and 19F NMR spectroscopy, we investigated the conformational dynamics of the Zika virus protease. Our findings suggest that allosteric inhibitors induce an open conformation while competitive inhibitors stabilize a closed conformation of the protease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Ziwei Yang, Yang Han, Shilei Ding, Wei Shi, Tongqing Zhou, Andres Finzi, Peter D. Kwong, Walther Mothes, Maolin Lu
Summary: Variants of concern of SARS-CoV-2 have mutations in the spike glycoprotein that make them more transmissible and reduce the effectiveness of COVID-19 vaccines and antibody therapies. Studies have shown that these variants have a higher propensity for open conformations accessible to the human ACE2 receptor, with slower transitions between accessible/bound states. This increased stability of the spike protein in open conformations provides insight into the adaptation strategies of SARS-CoV-2.
Article
Microbiology
Ziwei Yang, Yang Han, Shilei Ding, Wei Shi, Tongqing Zhou, Andres Finzi, Peter D. Kwong, Walther Mothes, Maolin Lu
Summary: The variants of concern of SARS-CoV-2 have mutations that enhance transmission and reduce the effectiveness of COVID-19 vaccines and treatments. These variants have a higher propensity to bind to the human receptor and exhibit slower transitions between receptor-bound states. These findings provide insights into the adaptation strategies of SARS-CoV-2.
Article
Biochemistry & Molecular Biology
Wesley B. Asher, Daniel S. Terry, G. Glenn A. Gregorio, Alem W. Kahsai, Alessandro Borgia, Bing Xie, Arnab Modak, Ying Zhu, Wonjo Jang, Alekhya Govindaraju, Li-Yin Huang, Asuka Inoue, Nevin A. Lambert, Vsevolod V. Gurevich, Lei Shi, Robert J. Lefkowitz, Scott C. Blanchard, Jonathan A. Javitch
Summary: Beta-arrestins are strongly autoinhibited in their basal state but can be activated by phosphorylated receptors and receptor agonism, releasing the beta-arrestin tail and allowing it to assume different conformations. The rate and efficiency of beta-arrestin activation depend on the phosphorylation pattern of the receptor and agonist-promoted receptor activation.
Article
Chemistry, Multidisciplinary
Stacey Wardenfelt, Xinyao Xiang, Mouzhe Xie, Lei Yu, Lei Bruschweiler-Li, Rafael Bruschweiler
Summary: This study utilizes a new method to investigate the dynamics of protein interactions with nanoparticles. The results indicate that the interaction between proteins and silica nanoparticles of different sizes is not significant, and the backbone dynamics are confined to sub-nanosecond timescales.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Elena Nemtseva, Dmitry Gulnov, Marina A. Gerasimova, Lev A. Sukovatyi, Ludmila P. Burakova, Natalya E. Karuzina, Bogdan S. Melnik, Valentina A. Kratasyuk
Summary: The study compared the unfolding pathways of two luciferases under urea conditions, finding that the unfolding pathway was the same but the P. leiognathi luciferase had more stable tertiary and secondary structures compared to the V. harveyi enzyme. The differences in fluorescence of the two proteins were associated with differences in the structure of the C-terminal domain of alpha-subunits leading to different quenching of tryptophan emissions. Time-resolved fluorescence technique was shown to be a more effective method for studying protein unfolding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Sowmya Indrakumar, Alina Kulakova, Pernille Harris, Gunther H. J. Peters
Summary: The conformational stability of human serum transferrin under varying pH values, salt concentrations, and excipient concentrations were investigated using molecular dynamics simulations. The findings were compared with small-angle X-ray scattering experiments. The results show that pH values and ion interactions play significant roles in the conformational changes of transferrin.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Bei Tong, Fang Tian, Peng Zheng
Summary: Titin, the largest protein in humans, plays a critical role in muscle's elasticity. The study investigates the mechanical stability of Ig domains and shows that the interdomain linker affects their stability in a complex and domain-specific manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Markus Zweckstetter
Summary: The AlphaFold2 method has shown the ability to accurately predict protein structures in solution, matching well with experimental data, and holds promise as a powerful tool for studying structural changes in proteins.
Article
Pharmacology & Pharmacy
Sandor Vaczi, Lilla Barna, Krisztian Laczi, Ferenc Tomosi, Gabor Rakhely, Botond Penke, Livia Fulop, Ferenc Bogar, Tamas Janaky, Maria A. Deli, Zsofia Mezei
Summary: This study examined the effects of sigma-1 receptor ligands on platelet and vascular eicosanoid synthesis. The results showed that these ligands can modify the synthesis of eicosanoids in platelets and vessels and play a role in multiple steps of arachidonic acid metabolism.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emoke Borbely, Viktoria Varga, Titanilla Szoegi, Ildiko Schuster, Zsolt Bozso, Botond Penke, Livia Fueloep
Summary: Alzheimer's disease, the most common form of dementia, is extensively studied for pharmacological interventions to slow its progression. Neuronal sigma-1 receptors (S1Rs) have been identified as potential targets for therapy, as S1R ligands show promise in mitigating the severity of symptoms and regulating neurogenesis. The selective S1R agonist PRE084 appears to be a promising therapeutic agent for AD, stimulating the proliferation and differentiation of hippocampal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ferenc Bogar, Livia Fulop, Botond Penke
Summary: Neurodegenerative diseases (NDDs) are characterized by progressive deterioration of cells and their networks in the nervous system. Currently, there are no treatments available to stop the progression of NDDs. Neuroinflammation has been a focus in drug development for NDDs. The Sigma-1 receptor (Sig-1R) is a potential target for NDD drug development, as its activation can provide neuroprotection and slow down the progression of NDDs.
Article
Biochemistry & Molecular Biology
Titanilla Szogi, Emoke Borbely, Ildiko Schuster, Zsolt Bozso, Miklos Santha, Melinda E. Toth, Botond Penke, Livia Fulop
Summary: This study examines the longitudinal alterations in neurogenesis, neuroinflammation, and AD pathology in a transgenic mouse model, and evaluates the potential beneficial effects of long-term P33 treatment on AD-specific neurological changes. The findings suggest that early pharmacological treatment may ameliorate neurological decline.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sandor Vaczi, Lilla Barna, Krisztian Laczi, Ferenc Tomosi, Gabor Rakhely, Botond Penke, Livia Fulop, Ferenc Bogar, Tamas Janaky, Maria A. Deli, Zsofia Mezei
Summary: S1R ligands regulate cellular functions and local blood circulation by influencing arachidonic acid metabolism. Sub-chronic, in vivo administration of S1R ligands in streptozotocin-induced diabetic rats had different effects, some of which were protective and some promoted the recovery of diabetes.
Article
Biochemistry & Molecular Biology
Maria Csilla Csanyi, Pal Salamon, Timea Feller, Tamas Bozo, Jolan Harsfalvi, Miklos S. Z. Kellermayer
Summary: The von Willebrand factor (VWF) is a multimeric glycoprotein that mediates platelet function at high shear. The shear-induced structural transitions of VWF have been studied through high-resolution quantitative analysis of gradually extended VWF. The structural hierarchy uncovered provides a spatial control mechanism for the complex functions of VWF.
Article
Biochemistry & Molecular Biology
Zsolt Csenki, Tibor Bartok, Illes Bock, Levente Horvath, Beata Lemli, Balazs Zoltan Zsido, Cserne Angeli, Csaba Hetenyi, Istvan Szabo, Bela Urbanyi, Melinda Kovacs, Miklos Poor
Summary: Fumonisins, including fumonisin B1 (FB1), are common food contaminants that can have harmful effects on humans and animals. Acylated metabolites of FB1, such as N-palmitoyl-FB1 and 5-O-palmitoyl-FB1, have higher toxicity compared to FB1. Our study investigated the interactions of these mycotoxins with human serum albumin and their toxic effects on zebrafish embryos. The findings suggest that palmitoyl-FB1 derivatives form stable complexes with albumin and have a greater toxic effect on zebrafish compared to FB1.
Article
Chemistry, Multidisciplinary
Janos Szebeni, Balint Kiss, Tamas Bozo, Keren Turjeman, Yael Levi-Kalisman, Yechezkel Barenholz, Miklos Kellermayer
Summary: Despite the success of mRNA-LNP Covid-19 vaccines, the nanoscale structures of these formulations are still not well understood. In this study, various microscopy techniques were used to analyze the nanoparticles in the vaccine and compare them with a well-characterized liposomal formulation. The results revealed important structural features of the mRNA-LNP that may be relevant for its in vivo activities.
Article
Physics, Applied
I. Banyasz, I. Rajta, V. Havranek, A. Mackova, A. J. Laki, M. S. Z. Kellermayer, Z. Szittner, S. Kurunczi, Sz. Novak, I. Szekacs, R. Horvath, M. Fried, G. U. L. Nagy
Summary: Handling of picoliter-to-nanoliter-scale volumes and objects is increasingly important in the field of life sciences. In this study, a method of generating picoliter-scale devices through direct writing on a ZEONOR copolymer surface using a high-energy medium-mass ion microbeam was introduced. Various microstructures were written in the sample using a 10.5MeV N4+ ion microbeam at different fluences. The best array was obtained by implanting annuli with inner and outer diameters of 10 and 11 μm, respectively, and a fluence of 7.8 x 10(12) ions/cm(2).
APPLIED PHYSICS LETTERS
(2023)
Article
Medicine, Research & Experimental
Orsolya Balazs, Agnes Dombi, Balazs Z. Zsido, Csaba Hetenyi, Katerina Valentova, Robert G. Vida, Miklos Poor
Summary: This study examined the inhibitory effects of several flavonoids and their metabolites on the XO enzyme. The sulfate metabolites showed stronger inhibitory effects on XO compared to the parent flavonoids, while the glucuronic acid derivatives were weaker inhibitors.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Balazs Zoltan Zsido, Bayartsetseg Bayarsaikhan, Rita Borzsei, Viktor Szel, Violetta Mohos, Csaba Hetenyi
Summary: Water plays a crucial role in various natural processes, and therefore molecular engineering must consider the structural and energetic effects of hydration. This review focuses on target-ligand interactions in drug design, particularly in biomolecules, but the methods and applications can be adapted to other areas of molecular complex engineering, including solid hydrates. The review discusses the determination of water structures, encompassing experimental approaches, theoretical calculations, and conceptual classifications. It also highlights the use of water models in calculating binding thermodynamics and performing computational ligand docking. The review concludes that theoretical approaches not only replicate or enhance experimental water structures but also provide essential insights into the contributions of individual water molecules, making them indispensable tools in molecular engineering.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Balazs Zoltan Zsido, Bayartsetseg Bayarsaikhan, Rita Borzsei, Csaba Hetenyi
Summary: This study introduces a new method called PepGrow, which uses docked histone fragments as seeds to grow the full peptide tails in the reader-binding pocket, enabling the efficient generation of atomic-resolution structures of histone-reader complexes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Alexander G. Bobylev, Elmira Yakupova, Liya G. Bobyleva, Nikolay Molochkov, Alexander A. Timchenko, Maria A. Timchenko, Hiroshi Kihara, Alexey D. Nikulin, Azat G. Gabdulkhakov, Tatiana N. Melnik, Nikita Penkov, Michail Y. Lobanov, Alexey S. Kazakov, Miklos Kellermayer, Zsolt Martonfalvi, Oxana Galzitskaya, Ivan M. Vikhlyantsev
Summary: The giant protein titin, found in striated and smooth muscles, undergoes nonspecific amyloid aggregation in vitro. The high-molecular-weight isoform of chicken smooth-muscle titin forms amorphous amyloid aggregates with a quaternary cross-beta structure. These aggregates do not affect the secondary structure of the protein and can partially disaggregate at higher ionic strengths. This study suggests that specific domains/segments of titin are involved in the amyloid aggregation process. Understanding amyloidogenesis could be expanded by studying titin as an object of interest.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Aida Nonn, Balint Kiss, Weria Pezeshkian, Thomas Tancogne-Dejean, Albert Cerrone, Miklos Kellermayer, Yuanli Bai, Wei Li, Tomasz Wierzbicki
Summary: A methodology combining experimental and simulation techniques was proposed to investigate the internal structure and mechanical properties of SARS-CoV-2. The elastic properties and fracture strength of the viral membrane were estimated, and the results showed a close association between membrane proteins and ribonucleoproteins. These findings provide valuable knowledge for the development of novel prevention and treatment methods.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Chemistry, Physical
Viktor Szel, Balazs Zoltan Zsido, Norbert Jeszenoi, Csaba Hetenyi
Summary: This article introduces a fast calculator QMH-L for estimating target-ligand binding thermodynamics data. QMH-L uses semi-empirical quantum mechanics calculation of binding enthalpy and a descriptor based on the elemental composition of the ligand. The method shows excellent performance in terms of computational efficiency and accuracy, and can be applied in drug design and molecular engineering projects.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)