Article
Biochemistry & Molecular Biology
Andres Manuel Vera, Albert Galera-Prat, Michal Wojciechowski, Bartosz Rozycki, Douglas Laurents, Mariano Carrion-Vazquez, Marek Cieplak, Philip Tinnefeld
Summary: Cellulose is a renewable and abundant organic molecule used for biofuel and chemical production. Cellulosomes, composed of multiple enzymes, display unmatched efficiency in degrading lignocellulosic substrates. By studying the cohesin-dockerin interaction, multiple binding modes and a prolyl isomerase-modulated allosteric control mechanism were discovered, providing a novel understanding of the structural plasticity and dynamics of cellulosomes.
Article
Biophysics
Michael Morse, Francesco Navarro Roby, Mansi Kinare, James McIsaac, Mark C. Williams, Penny J. Beuning
Summary: Single-stranded DNA-binding proteins (SSBs) play a crucial role in DNA repair and replication. This study investigated the binding of SSB to individual DNA molecules and the effect of DNA damage on binding conformation. The results showed that the presence of damaged nucleotides reduced the binding affinity of SSB, but did not affect its binding capability. These findings provide insights into the changes in genomic repair and replication processes under accumulating environmental damage.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Bei Liu, Orrin J. Stone, Michael Pablo, J. Cody Herron, Ana T. Nogueira, Onur Dagliyan, Jonathan B. Grimm, Luke D. Lavis, Timothy C. Elston, Klaus M. Hahn
Summary: The approach utilizes binder/tag to study the conformation of individual proteins during single particle tracking in living cells, allowing for the tracking of protein trajectory and conformation, and providing highly specific biosensors.
Article
Biochemistry & Molecular Biology
Koji Kitamura, Hidefumi Suzuki, Ryota Abe, Hidenori Inohara, Yasufumi Kaneda, Hidehisa Takahashi, Keisuke Nimura
Summary: This study reveals that the splicing factor SF3B2 plays a role in regulating transcription and RNA stability in head and neck squamous cell carcinoma. High SF3B2 expression is associated with poor prognosis and accelerated tumor growth. SF3B2 has a dual function in both transcription and RNA stability.
CELL AND BIOSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Benjamin R. Camel, Davis Jose, Katarina Meze, Anson Dang, Peter H. von Hippel
Summary: This study utilizes single-stranded DNA lattices and 2-AP probes to investigate the local interactions of DNA bases with the nucleic acid binding cleft of gp32 protein. By employing complementary spectroscopic approaches, the study characterizes these interactions at different levels of protein binding cooperativity and provides insights into how gp32 can manipulate the ssDNA chain during various processes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Inorganic & Nuclear
Wen-long Duan, Cong Ma, Jian Luan, Fang Ding, Feng Yan, Lei Zhang, Wen-Ze Li
Summary: A new type of dual-functional inhibitor based on metal-organic salts (MOSs) has been synthesized and evaluated for urease and nitrification inhibitory activities. The MOSs showed excellent nitrification inhibitory activity and MOS 1 demonstrated significant urease inhibitory activity. Evaluation of the inhibition rates and concentrations of the MOSs suggest that they are efficient and environmentally friendly inhibitors. Overall, the study highlights the potential of MOSs as dual-functional inhibitors for reducing nitrogen loss in agriculture soil.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Si-Hai Wu, Rong Yang, Bin Sun, Jian-Hong Tang, Zhong-Liang Gong, Junjie Ma, Lianhui Wang, Jieqing Liu, Dian-Xue Ma, Jiang-Yang Shao, Yu-Wu Zhong
Summary: Three tris-heteroleptic mononuclear Ru(II) complexes with dual fluorescence and phosphorescence were designed and used as ratiometric light-response probes for DNA, where two of the complexes exhibited stronger preference for calf thymus DNA. The interactions of these complexes with different DNAs were investigated by various methods, including spectroscopy and molecular modeling, providing valuable insights for potential applications in DNA sensing.
INORGANIC CHEMISTRY
(2021)
Article
Cell Biology
Nicoleta-Loredana Tanasie, Pilar Gutierrez-Escribano, Sigrun Jaklin, Luis Aragon, Johannes Stigler
Summary: SMC complexes, especially Smc5/6, play important roles in DNA replication and repair. This study used single-molecule microscopy to investigate the interaction between Smc5/6 and DNA. It was found that Smc5/6 forms oligomers that dynamically redistribute on dsDNA and statically bind to ssDNA. The study also generated ssDNA-dsDNA junctions to mimic structures in DNA repair intermediates or replication forks, and showed that Smc5/6 accumulates at these junction sites, stabilizes the fork, and promotes the retention of RPA. These findings provide insights into the enrichment of the complex at sites of replication stress and DNA lesions, and its role in coordinating downstream repair proteins.
Article
Chemistry, Multidisciplinary
Yuqing Xiong, Juan Zeng, Fei Xia, Qiang Cui, Xianming Deng, Xin Xu
Summary: This study characterized the conformational changes of SOS and Ras, especially for the substates of State 1 of HRasGTP·Mg2+, using extensive molecular dynamics simulation. Binding pockets on Ras and the ternary complexes with SOS were predicted, providing a structural foundation for future drug design.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Catarina Carmo, Joao Coelho, Rui D. Silva, Alexandra Tavares, Ana Boavida, Paola Gaetani, Leonardo G. Guilgur, Rui Goncalo Martinho, Raquel A. Oliveira
Summary: By monitoring ongoing transcription in Drosophila early embryos, the study reveals that eviction of nascent mRNAs from mitotic chromatin occurs after chromosome compaction and is driven by the SNF2 helicase-like protein Lodestar. In addition to the eviction of transcripts, Lodestar also cooperates with Topoisomerase 2 to ensure efficient sister chromatid resolution and mitotic fidelity.
Article
Polymer Science
Marcus Mueller
Summary: This study investigates the structure and dynamics of loops and bridges in the lamellar phase of symmetric ABA triblock copolymers, revealing a linear correlation between bridge fraction and the average variance of the first Rouse mode. The system is proposed to be a mixture of noninteracting loops and bridges with a two-state Markov dynamics. Multichain simulations show an extremely long relaxation time, which can be accelerated using the heterogeneous multiscale method.
Article
Biochemical Research Methods
Amy F. Chen, Benjamin Parks, Arwa S. Kathiria, Benjamin Ober-Reynolds, Jorg J. Goronzy, William J. Greenleaf
Summary: NEAT-seq is a tri-omics tool that allows profiling nuclear protein abundance, chromatin accessibility, and the transcriptome in single cells, enabling investigation of regulatory mechanisms. This technique helps to validate the regulatory activity of TFs and internally validate the impact of SNPs on gene regulation using NEAT-seq data.
Review
Chemistry, Multidisciplinary
Rubi Roy, Tasnim Ria, Debapriya RoyMahaPatra, Ugir Hossain Sk
Summary: Due to the multimodal character of cancer, inhibiting two targets simultaneously by a single molecule is an effective approach. Histone deacetylase (HDAC) has been investigated as a novel category of anticancer drug targets due to its crucial role. However, currently approved HDAC inhibitors have limited usage due to their low efficacy, nonselectivity, drug resistance, and toxicity. Therefore, HDACs with dual targeting ability have attracted attention. Combining HDAC inhibitors with other antitumor agents has proved advantageous to combat the nonselectivity and drug resistivity problems. Our review focuses on the impact of substituent effect and linker variation of HDAC-inhibitor-conjugated anticancer drugs.
Article
Multidisciplinary Sciences
Hannah Ochner, Sven Szilagyi, Moritz Edte, Tim K. Esser, Stephan Rauschenbach, Luigi Malavolti, Klaus Kern
Summary: Low-energy electron holography (LEEH) can explore the conformational space of proteins and distinguish different conformations of transferrin, indicating its viability for imaging function-related conformational changes in individual proteins.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Aleksandra Kieliszek, Maura Malinska
Summary: The study of the conformations of p-tert-butylcalix[8]-arene (TBC8) revealed the significant influence of different crystallization solvents on crystal structure and molecular conformations, with different conformations observed under different solvent conditions. Density functional theory calculations supported the experimental results, confirming the existence of different conformations under varying solvent conditions.
CRYSTAL GROWTH & DESIGN
(2021)
Article
Chemistry, Multidisciplinary
Rosario Vanella, Gordana Kovacevic, Vanni Doffini, Jaime Fernandez de Santaella, Michael A. Nash
Summary: This article reviews the new methods in enzyme engineering, focusing on enzyme cascade-based readout systems and reaction compartmentalization techniques. It summarizes the application of systematic scanning mutagenesis methods and DNA sequencing technologies in generating mutability landscapes. Additionally, the implementation of machine learning models for predicting enzyme phenotypic fitness from sequence is discussed. This overview can help researchers identify the important challenges in advancing the field of enzyme engineering.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Zhaowei Liu, Rodrigo A. Moreira, Ana Dujmovic, Haipei Liu, Byeongseon Yang, Adolfo B. Poma, Michael A. Nash
Summary: Using single-molecule AFM force spectroscopy in combination with click chemistry, the mechanical interactions between anticalin and its target CTLA-4 were studied. Results showed that pulling from different anchor residues significantly affected rupture forces and dissociation rates. Molecular dynamics simulations revealed a geometric dependency of mechanostability.
Article
Microbiology
Viviana G. Correia, Filipa Trovao, Benedita A. Pinheiro, Joana L. A. Bras, Lisete M. Silva, Claudia Nunes, Manuel A. Coimbra, Yan Liu, Ten Feizi, Carlos M. G. A. Fontes, Barbara Mulloy, Wengang Chai, Ana Luisa Carvalho, Angelina S. Palma
Summary: A multi-gene polysaccharide utilization locus (PUL) targeting mixed-linkage beta 1,3-1,4-glucans has been identified in prominent members of Bacteroidetes in the human gut, which plays a crucial role in promoting a healthy microbiota and as potential prebiotics. The BoSGBP(MLG)-A protein shows unique binding specificity towards beta 1,3-1,4-gluco-oligosaccharides, with interactions characterized by a complex hydrogen bonding network and specific interactions with ordered water molecules. Understanding the molecular mechanisms of carbohydrate recognition by commensal bacteria like Bacteroidetes can provide insights into modulating the microbiome for promoting human health.
MICROBIOLOGY SPECTRUM
(2021)
Article
Veterinary Sciences
Diogo Coelho, Cristina M. Alfaia, Paula A. Lopes, Jose M. Pestana, Monica M. Costa, Rui M. A. Pinto, Joao M. Almeida, Olga Moreira, Carlos M. G. A. Fontes, Jose A. M. Prates
Summary: This study assessed the impact of a high dietary level of Chlorella vulgaris with and without carbohydrase mixtures on the health and liver metabolism of pigs. The results showed that the dietary level of C. vulgaris affected several blood parameters of finishing pigs and increased their susceptibility to infection diseases. The dietary supplementation with carbohydrase mixtures decreased some blood parameters. Additionally, feeding C. vulgaris increased the hepatic content of n-3 polyunsaturated fatty acids in pigs.
RESEARCH IN VETERINARY SCIENCE
(2022)
Review
Biophysics
Fanny Risser, Ivan Urosev, Joanan Lopez-Morales, Yang Sun, Michael A. Nash
Summary: The coagulation cascade is a series of molecular events in blood with clinical significance. Fibrinogen, a key player in coagulation, undergoes processing by thrombin proteases and forms insoluble fibrin clots at wound sites. Fibrin acts as a structural biomaterial, inhibiting fluid flow and maintaining hemostasis. Due to its clinical importance, fibrin is being studied as a potential molecular target for coagulation therapies. This topical review summarizes the current understanding of the coagulation cascade from a molecular, structural, and biophysical perspective and discusses the latest advancements in directed evolution and molecular engineering of fibrin-targeted proteins and polymers for coagulation modulation.
BIOPHYSICAL REVIEWS
(2022)
Article
Biochemical Research Methods
Joanan Lopez-Morales, Rosario Vanella, Gordana Kovacevic, Mariana Sa Santos, Michael A. Nash
Summary: We developed a tunable display platform that modulates the avidity of Aga2-fusion proteins on the yeast cell wall by controlling the concentration of the inducer. By regulating the copy number of displayed proteins, we demonstrated the effects of tunable avidity levels on cell adhesion and enzyme activity.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Chemistry, Analytical
Jaime Fernandez De Santaella, Jin Ren, Rosario Vanella, Michael A. Nash
Summary: We developed an enzyme cascade with horseradish peroxidase-based readout to screen human arginase-1 (hArg1) activity. The cascade combined four enzymes and generated colorimetric or fluorescent signals in response to hArg1 activity. By screening a curated hArg1 library, we identified a variant with enhanced catalytic turnover rate compared to wild type. Our assay is scalable and suitable for high-throughput screening and drug candidate testing for arginase inhibition.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Haipei Liu, Zhaowei Liu, Mariana Sa Santos, Michael A. A. Nash
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding and mechanical properties. However, the traditional method of immobilization using lysine residues results in a heterogeneous distribution of tether positions. In this study, we compared lysine-based immobilization to site-specific immobilization using genetically encoded peptide tags (ybbR). Our results showed that lysine-based immobilization led to signal deterioration and incorrect classification of unfolding pathways. We also developed a mixed immobilization approach that partially recovered specific signals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Joanan Lopez-Morales, Rosario Vanella, Tamara Utzinger, Valentin Schittny, Julia Hirsiger, Michael Osthoff, Christoph T. Berger, Yakir Guri, Michael A. Nash
Summary: The emergence of the SARS-CoV-2 Omicron variant has changed patient risk profiles and the course of the COVID-19 pandemic. Therefore, there is a need for sensitive serological tests that can analyze patient IgG responses to multiple variants.
Article
Chemistry, Multidisciplinary
Christoph Kung, Rosario Vanella, Michael A. Nash
Summary: Engineering catalytic and biophysical properties of enzymes is essential for their applications in biomedical and industrial fields. In this study, a high-throughput screening and directed evolution strategy was developed to enhance the performance of an enzyme called d-Amino acid oxidase, which is a candidate for cancer therapy. By using single-cell hydrogel encapsulation and fluorescence activated cell sorting (FACS), variants with improved substrate binding affinity were isolated and characterized. This study highlights the difficulty in predicting allosteric sites and the advantages of scalable library screening technologies for evolving catalytic enzymes.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Vanni Doffini, Haipei Liu, Zhaowei Liu, Michael A. Nash
Summary: This study reports the application of machine learning techniques to classify and analyze protein unfolding trajectories. It demonstrates the potential of machine learning to accelerate data analysis and generate new insights.
Article
Biochemistry & Molecular Biology
Fanny Risser, Joanan Lopez-Morales, Michael A. Nash
Summary: This study investigates the susceptibility of Staphylococcus aureus MSCRAMMs to proteolytic digestion by human thrombin, plasmin, and plasmin/SAK complexes. The study reveals that MSCRAMMs are highly resistant to proteolysis and that SAK binding to plasmin enhances this resistance.
ACS BIO & MED CHEM AU
(2022)
Article
Chemistry, Multidisciplinary
Haipei Liu, Zhaowei Liu, Byeongseon Yang, Joanan Lopez Morales, Michael A. Nash
Summary: This study investigates how the stability of sacrificial domains in adhesive polyproteins can be tuned to maximize mechanical work dissipation, serving as an adhesion strategy by bacteria.
Article
Agriculture, Dairy & Animal Science
Monica M. Costa, Luis B. Pio, Pedro Bule, Vania A. Cardoso, Marlene Duarte, Cristina M. Alfaia, Diogo F. Coelho, Joana A. Bras, Carlos M. G. A. Fontes, Jose A. M. Prates
Summary: This study evaluated the potential of an enzyme called ulvan lyase to degrade the cell walls of green macroalgae and release nutritive compounds. The results showed that ulvan lyase was the most efficient enzyme in disrupting the cell walls and promoting the release of reducing sugars and monosaccharides. However, there was no significant release of fatty acids, proteins, or pigments. These findings suggest that ulvan lyase has the potential to enhance the bioaccessibility of bioactive products from green macroalgae for use in the feed industry.
Article
Biophysics
Mariana Sa Santos, Haipei Liu, Valentin Schittny, Rosario Vanella, Michael A. Nash
Summary: Here, we present a method that allows for the direct comparison between cell adhesion strength at the population level and single-molecule receptor-ligand rupture mechanics using yeast surface display. The developed high-throughput yeast adhesion assay and atomic force microscope single-molecule force spectroscopy successfully identified correlations between single-molecule rupture force distributions and population adhesion strength. This method can accelerate research on mechanostable receptor-ligand complexes and receptor-mediated cell adhesion.
BIOPHYSICAL REPORTS
(2022)
