Article
Chemistry, Multidisciplinary
Tzu-Yi Tai, Fanrui Sha, Xiaoliang Wang, Xingjie Wang, Kaikai Ma, Kent O. Kirlikovali, Shengyi Su, Timur Islamoglu, Satoshi Kato, Omar K. Farha
Summary: This study presents the first systematic investigation on the thermodynamics of protein immobilization in metal-organic frameworks (MOFs). It demonstrates that MOFs provide a hydrophobic stabilizing microenvironment for proteins, leading to an entropically driven encapsulation process. Among a series of Zr-MOFs, pyrene-based NU-1000 exhibits the most favorable encapsulation process for insulin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biotechnology & Applied Microbiology
Shams T. A. Islam, Jie Zhang, Fabio Tonin, Renske Hinderks, Yanthi N. Deurloo, Vlada B. Urlacher, Peter-Leon Hagedoorn
Summary: Lignin valorization through laccase catalysis can release aromatic products, but different enzymes exhibit significant variations in conversion efficiency and rate. Trametes versicolor laccase follows Michaelis-Menten kinetics in converting Kraft lignin, with specific thermodynamic and kinetic parameters, making it a promising tool for guiding enzymatic lignin valorization strategies.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Chemistry, Physical
Pablo F. Garrido, Margarida Bastos, Adrian Velazquez-Campoy, Alfredo Amigo, Philippe Dumas, Angel Pineiro
Summary: The injection of air into an isothermal titration calorimeter's sample cell allows for accurate determination of the surface tension of the target liquid, despite the periodic contribution from bubbles. The new algorithm successfully identifies and analyzes these contributions, improving the analysis of calorimetric signals.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Review
Pharmacology & Pharmacy
Iago Dillion Lima Cavalcanti, Francisco Humberto Xavier Junior, Nereide Stela Santos Magalhaes, Mariane Cajuba de Britto Lira Nogueira
Summary: Isothermal titration calorimetry (ITC) is a technique for evaluating the thermodynamic profiles of connection between two molecules, allowing the experimental design of nanoparticles systems with drugs and/or biological molecules. In the field of pharmaceutical nanotechnology, ITC has been increasingly used to understand the interaction mechanisms in the formation of nanoparticles and the behavior of nanocarriers in in vivo studies. This technique provides quick and easy results to optimize the formulation process of nano-systems.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Thermodynamics
Ziga Medos, Isidora Cobanov, Marija Bester-Rogac, Bojan Sarac
Summary: This research paper examines the issues associated with power compensation isothermal titration calorimetry, highlighting the possibility of obtaining different enthalpy values with different instruments and setting parameters. It emphasizes that modern calorimeters' dynamic power compensation mode may lead to overcompensation of heat effects, resulting in experimental results heavily reliant on chosen parameters. To avoid these problems, the paper suggests checking raw signals and conducting experiments with low or disabled power compensation when observing switching effects.
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
(2021)
Article
Biochemistry & Molecular Biology
Adam Jugl, Miloslav Pekar
Summary: The interactions between hyaluronan and cecropin B were investigated using high-resolution ultrasonic spectroscopy and isothermal titration calorimetry. The study found that the molecular weight of hyaluronan played a significant role in the interactions, particularly the transition between different conformations. In water, interactions were saturated at a molar charge ratio of 1.5, possibly due to steric hinderance or functional group interactions. However, in PBS, no interactions were observed, regardless of the molecular weight of hyaluronan, indicating that the interactions were suppressed at higher ionic strength.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Fanrui Sha, Tzu-Yi Tai, Madeleine A. Gaidimas, Florencia A. Son, Omar K. Farha
Summary: Isothermal titration calorimetry (ITC) is a technique for measuring the thermodynamic parameters of binding events, which has applications not only in biological macromolecules but also in synthetic systems like metal-organic frameworks (MOFs). Utilizing ITC in MOFs can provide insights into small molecule adsorption mechanisms and the formation of MOF-based composite materials through non-covalent interactions, with specific experimental considerations discussed. Furthermore, underexplored research directions related to MOFs that could benefit from ITC are highlighted.
Article
Biochemistry & Molecular Biology
Alexandra D. Brown, Connor Cranstone, Denis J. Dupre, David N. Langelaan
Summary: The study investigates the interaction between β-catenin and CBP/p300, and determines that the C-terminal region of β-catenin binds to the TAZ1 and TAZ2 domains of CBP/p300. The results provide insights into the gene regulation mechanism of β-catenin and offer a framework for developing methods to block β-catenin dependent signaling.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Polymer Science
Jacek J. Walkowiak, Rohit Nikam, Matthias Ballauff
Summary: The effective charge of highly charged polyelectrolytes is significantly lowered by a condensation of counterions. This effect is more pronounced for divalent ions. Our study on dendritic polyglycerol sulfate (dPGS) demonstrates that the interactions between dPGS and divalent ions (Mg2+ and Ca2+) show no ion specificity but clear competition between monovalent and divalent ions. These findings support the latest theoretical studies and indicate the sequential replacement of monovalent ions with divalent ions.
Article
Biochemistry & Molecular Biology
Robert Kerep, Tino Seba, Valentina Borko, Tin Weitner, Toma Keser, Gordan Lauc, Mario Gabricevic
Summary: Human serum alpha-1 acid glycoprotein is involved in the binding and transport of many drugs. Sialic acid groups play a major role in drug binding. The study found that different sialylation can result in different binding affinities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Liang Ma, Zeyue Gao, Jiegen Wu, Bijunyao Zhong, Yuchen Xie, Wen Huang, Yihan Lin
Summary: The coactivator p300 can dynamically coordinate its functions by forming clusters with transcription factors, enabling spatially defined activation of its catalytic activity. This co-condensation mechanism modulates the transcriptional initiation rate and burst duration of target genes, contributing to nonlinear gene regulation. The results suggest a mechanism where TF and p300 co-condensation contributes to transcriptional bursting regulation and cooperative gene control.
Article
Chemistry, Applied
Wei Liao, Emilie Dumas, Abdelhamid Elaissari, Adem Gharsallaoui
Summary: This study investigated the formation mechanism of multilayer emulsions in oil-in-water systems by using isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) techniques. The results showed that ITC could provide more accurate information about the polymer concentration effect. The titration experiment confirmed that low methoxyl pectin (LMP) mainly bound sodium caseinate (CAS)-coated droplets through electrostatic forces, and stable multilayer emulsions were obtained by titrating CAS-stabilized droplets into LMP.
FOOD HYDROCOLLOIDS
(2023)
Article
Biochemistry & Molecular Biology
Mimosa Sillanpaa, Marica T. T. Engstroem, Petri Taehtinen, Rebecca J. J. Green, Jarmo Kapyla, Anu Nareaho, Maarit Karonen
Summary: Plant tannins have anthelmintic and antiparasitic activities and can be used as complementary nutrients alongside commercial anthelmintics. The interactions between tannins and anthelmintics are limited and can have both synergistic and antagonistic effects depending on the tannin type and method used. Hydrolysable tannins can directly interact with the anthelmintic thiabendazole, and this interaction is strengthened by increasing the number of free galloyl groups and the overall molecular flexibility of tannins.
Article
Chemistry, Applied
Paola Peluso, David Landy, Lamia Nakhle, Roberto Dallocchio, Alessandro Dessi, Sulaiman Krait, Antonio Salgado, Bezhan Chankvetadze, Gerhard K. E. Scriba
Summary: The complex formation between daclatasvir and gamma-CD or TM-beta-CD was studied using isothermal titration calorimetry and molecular modeling. The results showed that a 2:1 complex was predominantly formed with gamma-CD, while a 1:1 complex was formed to a lesser extent. In contrast, the TM-beta-CD complex had a stoichiometry of 1:1. The complex formation with gamma-CD did not require dissociation of the daclatasvir dimer and had a binding constant of 1.67x10^7 M-2, while the weak TM-beta-CD complex required dissociation of the daclatasvir dimer and had a binding constant of 371 M-1.
CARBOHYDRATE POLYMERS
(2023)
Article
Chemistry, Physical
Mathilde Coquil, Nathalie Boubals, Magali Duvail, Marie-Christine Charbonnel, Jean-Francois Dufreche
Summary: Despite the challenges in describing liquid-liquid extraction due to various organization phenomena, a new methodology combining microcalorimetric measurements and molecular modeling has been proposed to better understand the interactions in these complex fluids.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemistry & Molecular Biology
Amrinder Singh, Maria A. Martinez-Yamout, Peter E. Wright, H. Jane Dyson
Summary: NF-kappa B is a central mediator in cellular signaling pathways, which remains sequestered in the cytoplasm in complex with I kappa B alpha under resting conditions. Activation of NF-kappa B involves phosphorylation, ubiquitination, and degradation of I kappa B alpha, leading to its translocation to the nucleus. A long noncoding RNA, NKILA, was found to modulate the NF-kappa B signaling circuit by interacting with the NF kappa B-I kappa B alpha complex in the cytoplasm.
Article
Multidisciplinary Sciences
Rebecca B. Berlow, H. Jane Dyson, Peter E. Wright
Summary: Intrinsically disordered proteins compete for binding to common regulatory targets to carry out their biological functions. The activation domains of HIF-1 alpha and CITED2 function as a unidirectional, allosteric molecular switch to control transcription of adaptive genes. The mechanistic details of this molecular switch were characterized through NMR spectroscopy and biophysical methods, revealing the contributions of individual binding motifs in CITED2. These findings provide insight into the complexity of molecular interactions involving disordered proteins and how they compete for occupancy of common targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Daisuke Tashiro, Shunji Suetaka, Nao Sato, Koji Ooka, Tomoko Kunihara, Hisashi Kudo, Junichi Inatomi, Yuuki Hayashi, Munehito Arai
Summary: Human epidermal growth factor receptors (HER/ERBB) play a vital role in cell proliferation and cancer, but overexpression can cause cancer. Herstatin, an alternative splice variant of HER2, has been identified as a tumor suppressor. This study reveals that a specific domain of herstatin, called Int8, is intrinsically disordered but has a residual helical structure. The research also suggests that a mutant form of Int8, R371I, that is defective in binding to HER2, may lead to the loss of its tumor-suppressive activity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Koji Ooka, Runjing Liu, Munehito Arai
Summary: The WSME model is a promising statistical mechanical model that can calculate the free-energy landscapes of proteins, providing a comprehensive understanding of protein folding mechanisms and structure stability. By predicting protein folding mechanisms and associated conformational changes, this model is expected to be useful in both basic research and applications.
Article
Biochemistry & Molecular Biology
Alexander S. Krois, Sangho Park, Maria A. Martinez-Yamout, H. Jane Dyson, Peter E. Wright
Summary: The structure and interactions of the C-terminal region of p53 protein have been studied. Full-length p53 constructs were generated using trans-intein splicing and isotopically labeled for NMR analysis. This study provides high-resolution insights into the behavior of the C-terminal domains within the full-length protein and the molecular basis of its interactions with DNA.
Article
Chemistry, Physical
Derrick W. Meinhold, Daniel J. Felitsky, H. Jane Dyson, Peter E. Wright
Summary: The early events in protein folding, especially in the unfolded state, are not well understood. The study used NMR experiments to investigate the transient local collapse events in the unfolded-state of apomyoglobin. The findings suggest that there are pH-dependent transient intramolecular contacts occurring at a microsecond to millisecond time scale. The rapid and concomitant chain collapse and secondary structure formation were observed in the early folding intermediates.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Review
Biotechnology & Applied Microbiology
Yuuki Hayashi, Munehito Arai
Summary: The use of biologically produced alkanes as an alternative to petroleum has gained significant attention. The discovery of the alkane synthesis pathway in cyanobacteria and the proteins involved, acyl-(acyl carrier protein [ACP]) reductase (AAR) and aldehyde deformylating oxygenase (ADO), has opened up new possibilities for alkane production through genetic modification. This review summarizes recent findings on the structures and catalytic mechanisms of AAR and ADO, outlines the complex formation and efficient transfer of insoluble aldehydes between AAR and ADO, and describes advancements in protein engineering studies to improve alkane production in genetically engineered microorganisms. The role of alkanes in cyanobacteria and future perspectives for bioalkane production using AAR and ADO are also discussed.
MICROBIAL CELL FACTORIES
(2022)
Review
Chemistry, Multidisciplinary
H. Jane Dyson, Peter E. Wright
Summary: It is difficult to assess the role of individual mentors in the development of important ideas. However, in the case of the realization that proteins can be functional without stable folding, the influence of Richard Lerner and the collaborative work in the 1980s on immunogenic peptides provided a foundation for understanding the nature of polypeptides in water solutions. This led to the formulation and development of the concept of intrinsic disorder in proteins, and the recognition of its functional advantage in cellular processes.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Microbiology
Daiki Matsuike, Yuhei O. Tahara, Takahiro Nonaka, Heng Ning Wu, Tasuku Hamaguchi, Hisashi Kudo, Yuuki Hayashi, Munehito Arai, Makoto Miyata
Summary: In this study, the function and structure of the surface protein Gli123 in Mycoplasma mobile were investigated. It was found that Gli123 has two distinct globular and rod-like structures, and it plays a crucial role in the assembly of the surface gliding machinery through the evolution of repetitive lipoprotein units.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Multidisciplinary Sciences
Nao Sato, Shunji Suetaka, Yuuki Hayashi, Munehito Arai
Summary: The researchers designed a KIX inhibitor by performing theoretical saturation mutagenesis and found that the T2857W mutant of the MLL TAD peptide had the highest binding affinity for KIX. This peptide also showed a significant inhibitory effect on the KIX-MLL interaction. This approach may be useful for developing helical peptides that can inhibit protein-protein interactions involved in disease progression.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Takahisa Suzuki, Masataka Yoshimura, Hiroki Hoshino, Keiji Fushimi, Munehito Arai, Rei Narikawa
Summary: This study identified a unique variant molecule of CBCR GAF domain that showed far-red/blue reversible photoconversion by introducing a second Cys residue near the chromophore. This discovery provides insights into the spectral tuning mechanism of CBCRs and contributes to tool development.
Article
Multidisciplinary Sciences
Koji Ooka, Munehito Arai
Summary: Recent advancements in using deep neural networks for accurate protein structure prediction have made significant progress in solving the structure prediction aspect of the protein folding problem. However, predicting the detailed mechanisms of protein folding into specific native structures remains challenging, especially for multidomain proteins that make up the majority of proteomes. In this study, a simple structure-based statistical mechanical model was developed to incorporate nonlocal interactions that drive the folding of multidomain proteins. The model successfully predicted protein folding processes consistent with experimental results, overcoming limitations in protein size and shape. Additionally, slight modifications allowed for the prediction of disulfide-oxidative and disulfide-intact protein folding, providing insight into folding mechanisms beyond experimental reproduction. Therefore, these physics-based models enable accurate prediction of protein folding mechanisms with low computational complexity and pave the way for solving the folding process aspect of the protein folding problem.
NATURE COMMUNICATIONS
(2023)
