Article
Biochemistry & Molecular Biology
Gary S. Howarth, Ann E. McDermott
Summary: This study investigates the structure of the cytosolic N- and C-termini of the pH-activated bacterial potassium channel KcsA. The researchers used HR-MAS and fractional deuteration as tools to study these poorly resolved regions. They found that the C-terminus transitions from a rigid structure to a more dynamic structure in acidic solution, and made previously unreported assignments of residues in the C-terminus of lipid-embedded channels.
Article
Multidisciplinary Sciences
C. Kevin Song, V. Andrew Molina, Ruofan Chen, A. Isabelle Gagnon, Young Hoon Koh, Benoit Roux, R. Tobin Sosnick
Summary: The dynamics and folding of potassium channel pore domain monomers are intertwined with tetramer assembly kinetics. Monomers can adopt nonnative conformations but can be locked into a native-like conformation through engineered disulfide bonds. Folding occurs via fast and slow routes within the protein-dense region, with constructs bearing disulfide bonds favoring the faster pathway. Despite its tetrameric nature, the folding process is concentration independent, with the rate-limiting step occurring after monomer association in the protein-dense region.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Physical
Sergio Perez-Conesa, Eric G. Keeler, Dongyu Zhang, Lucie Delemotte, Ann E. McDermott
Summary: The pH-gated prokaryotic channel KcsA has been extensively studied as the first potassium channel with an x-ray structure determined, but questions related to the allosteric coupling between its gates remain open. Solid-state nuclear magnetic resonance (SSNMR) can provide insights into the molecular basis of activation mechanisms by studying the wild-type protein under activating conditions, and simulation techniques such as molecular dynamics (MD) simulations can help determine the activated state captured in SSNMR experiments.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Jin Wook Cha, Xing Jin, Sihyang Jo, Yong Jin An, Sunghyouk Park
Summary: Metabolomic isotopic tracing using NMR can provide valuable flux information for understanding drug mechanisms. The newly developed 2D heteronuclear NMR experiment allows for quantitative analysis of multiplets with high sensitivity and resolution. When applied to an old chemotherapeutic drug, it confirmed conventional mechanisms while also identifying a new metabolic pathway contributing to the drug's broad pharmacological activities.
Article
Multidisciplinary Sciences
Anna Hojka-Osinska, Aleksander Chlebowski, Joanna Grochowska, Ewelina P. Owczarek, Kamila Affek, Kamila Klosowska-Kosicka, Roman J. Szczesny, Andrzej Dziembowski
Summary: Processive exoribonucleases play a crucial role in RNA decay and have complex genetic interactions with diverse pathways of RNA metabolism. Functional differences between nuclear DIS3 and cytoplasmic DIS3L in RNA metabolism were identified in human cells.
Article
Chemistry, Multidisciplinary
Eric Girard, Pedro Lopes, Michael Spoerner, Anne-Claire Dhaussy, Thierry Prange, Hans Robert Kalbitzer, Nathalie Colloc'h
Summary: In this study, the researchers used high pressure crystallography to investigate the allosteric transitions of Ras protein. They found that pressure can shift the equilibria between different conformational states, providing insight into the structural plasticity involved in Ras protein's allosteric equilibria.
Article
Construction & Building Technology
Xiuyu Zhu, Dongming Yan, Hongyuan Fang, Shikun Chen, Hailong Ye
Summary: The geopolymerization process in geopolymer cement affects mechanical properties and chemical durability by forming alkaline aluminosilicate gels of varying degrees of polymerization. Vacuum dehydration is demonstrated as an efficient method to halt geopolymerization for NMR analysis. Four stages of geopolymerization are identified, each differentiated by reaction duration and Q(m)(nAl) evolution, providing new insights into the mechanisms affected by free water loss.
CONSTRUCTION AND BUILDING MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Yingxue Zhang, Eid Alshammari, Jacob Sobota, Alexander Yang, Chunying Li, Zhe Yang
Summary: SMYD5 is a unique protein lysine methyltransferase with MYND and SET domains. AlphaFold structures are reliable for understanding its structure and function, revealing novel features such as the N-terminal sequence and structural flexibility.
Article
Chemistry, Physical
Evren Ozarslan, Cem Yolcu, Alfredo Ordinola, Deneb Boito, Tom Dela Haije, Mathias Hojgaard Jensen, Magnus Herberthson
Summary: The diffusion process is characterized by the diffusion propagator, which is sensitive to boundaries and structure within pores. This study proposes a special sequence of magnetic field gradient pulses to fully characterize the diffusion process, allowing for mapping structural dispersity and determining both the shape and dynamics within the pore.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Multidisciplinary Sciences
Diego F. Gauto, Pavel Macek, Duccio Malinverni, Hugo Fraga, Matteo Paloni, Iva Sucec, Audrey Hessel, Juan Pablo Bustamante, Alessandro Barducci, Paul Schanda
Summary: This study reveals the critical role of a flexible loop in the function of an aminopeptidase and demonstrates the ability of magic-angle spinning NMR to provide atomic-level quantitative insights in a very large complex.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Dongyu Zhang, Gary S. Howarth, Lia A. Parkin, Ann E. McDermott
Summary: The membrane environment, including specific lipid characteristics, plays important roles in the folding, stability, and gating of the prokaryotic potassium channel KcsA. The findings suggest that anionic lipids may promote channel inactivation.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Review
Biochemistry & Molecular Biology
Toshio Ando
Summary: High-speed atomic force microscopy (HS-AFM) can directly visualize the dynamic structure of intrinsically disordered proteins (IDPs) and reveal their unique functions. This technique does not alter the dynamic structure of IDPs and can estimate the number of amino acids in fully disordered regions from images. In addition, the dumbbell-like structure observed on IDPs has important functional relevance.
Article
Chemistry, Physical
Deyun Wang, Yongchao Su, Kang Chen
Summary: Knowledge of molecular rotational dynamics is crucial for understanding solution NMR spectroscopy. The study finds that the observed NMR signals in micelles contradict the viscosity effects predicted by the SED equation. By measuring the spin relaxation rates of a drug dissolved in micelles, the study demonstrates fast rotational dynamics of the solute molecules inside micelles, highlighting the role of intermolecular interactions rather than solvent viscosity in governing molecular motion.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Kyoung Ho Jung, Sunghark Kwon, Chang Min Kim, Jun Hyuck Lee, Hyun Ho Park
Summary: The study unveiled the hexameric crystal structure of MurG from Acinetobacter baumannii, a human pathogen, being the first homo-oligomeric structure described in the MurG family and the Mur family. This finding helps understand the molecular assembly mechanism of MurG and offers potential clues for developing new antibiotic targets.
Article
Chemistry, Physical
Daniel M. Dawson, Laurie E. Macfarlane, Mahrez Amri, Richard Walton, Sharon E. Ashbrook
Summary: A study was conducted on the calcination process of GaPO-34 gallophosphate, revealing differences between materials prepared with 1-methylimidazole and pyridine as the structure-directing agent. This study utilized a combination of experimental techniques to analyze the intermediate structures and phase transitions during dehydrofluorination.
JOURNAL OF PHYSICAL CHEMISTRY C
(2021)
Article
Chemistry, Multidisciplinary
Marin Yokomine, Jumpei Morimoto, Yasuhiro Fukuda, Yota Shiratori, Daisuke Kuroda, Takumi Ueda, Koh Takeuchi, Kouhei Tsumoto, Shinsuke Sando
Summary: In this study, oligo(N-methylalanine) (oligo-NMA) is proposed as a peptide-based molecular scaffold with a minimal structure and a high density of functionalizable sites. Oligo-NMA forms a defined shape in water without hydrogen-bonding networks or ring constraints. It can be easily functionalized on the nitrogens and a-carbons. The usefulness of oligo-NMA is demonstrated by the design of protein ligands.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Takeru Sagae, Mariko Yokogawa, Ryoichi Sawazaki, Yuichiro Ishii, Nao Hosoda, Shin-ichi Hoshino, Shunsuke Imai, Ichio Shimada, Masanori Osawa
Summary: This study investigated the functional mechanisms of Paip2A in translation repression. The findings reveal that Paip2A can bind to the poly(A)-binding interfaces of PABPC1’s RRM2 and RRM3 regions and effectively dissociate PABPC1 from poly(A). These insights may contribute to the development of novel anticancer and antiviral drugs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Takumi Ueda, Shunsuke Imai, Ichio Shimada
Summary: GPCRs are important receptors for neurotransmitters and hormones, and they are targeted by a significant number of modern drugs. Although the number of GPCR crystal structures has increased rapidly, they alone cannot fully explain the key features of GPCR signaling. Recent studies have shown that GPCRs are structurally dynamic and can adopt multiple conformations. NMR methods provide valuable insights into the dynamics of GPCRs in solution, despite the challenges posed by their instability and large molecular weights.
JOURNAL OF MAGNETIC RESONANCE
(2022)
Article
Biochemistry & Molecular Biology
Koh Takeuchi, Yoshiki Ikeda, Miki Senda, Ayaka Harada, Koji Okuwaki, Kaori Fukuzawa, So Nakagawa, Hong Yang Yu, Lisa Nagase, Misaki Imai, Mika Sasaki, Yu-Hua Lo, Doshun Ito, Natsuki Osaka, Yuki Fujii, Atsuo T. Sasaki, Toshiya Senda
Summary: Unlike most kinases, PI5P4K8 utilizes GTP as a phosphate donor and regulates cell growth under stress. It has evolved GTP responsiveness through the acquisition of a specific recognition motif.
Article
Biochemistry & Molecular Biology
Wenchao Zhu, Shiori Takeuchi, Shosei Imai, Tohru Terada, Takumi Ueda, Yusuke Nasu, Takuya Terai, Robert E. Campbell
Summary: Molecular fluorescent indicators based on chemigenetic combination of synthetic ion-recognition motifs and protein-based fluorophores are versatile tools for dynamic imaging of biological systems. This design enables the development of chemigenetic indicators with ion or molecular specificities that have not been realized with fully protein-based indicators.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Koh Takeuchi, Miki Senda, Yoshiki Ikeda, Koji Okuwaki, Kaori Fukuzawa, So Nakagawa, Mika Sasaki, Atsuo T. Sasaki, Toshiya Senda
Summary: Through 4 billion years of evolution, various mutations have led to the emergence of de novo genes that encode proteins with novel properties essential for cellular functions. However, the molecular processes underlying how a new protein function evolves are largely speculative. Recent evidence suggests that phosphatidylinositol 5-phosphate 4-kinase beta (PI5P4K beta) evolved into a GTP sensor from an ATP-utilizing kinase in mammalian cells through a mutation in its nucleotide base recognition sequence. This evolutionary transition gave rise to GTP sensing activity, which is crucial for cellular metabolism and tumorigenic activity.
Letter
Chemistry, Multidisciplinary
Dennis Shi, Sho Toyonaga, Daniel G. Anderson
Summary: A targeted lipid nanoparticle was developed to deliver RNA to HSCs in vivo, without the need for stem cell harvest or culture. In addition, gene editing using Cre recombinase mRNA was shown to be effective in editing a large percentage of HSPCs in vivo, while maintaining their stemness and functionality.
Article
Multidisciplinary Sciences
Jun-ichi Sugiyama, Yuji Tokunaga, Mafumi Hishida, Masahito Tanaka, Koh Takeuchi, Daisuke Satoh, Masahiko Imashimizu
Summary: This study investigates the collective dynamics of protein and water molecules in the sub-terahertz frequency region and their influence on the chemical processes in protein-water systems. The results show that sub-terahertz irradiation gradually decreases the dielectric permittivity of the protein solution by reducing the polarization of water molecules. These findings are important for studying hydration-mediated protein functions based on sub-terahertz irradiation.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yuki Hosono, Satoshi Uchida, Moe Shinkai, Chad E. Townsend, Colin N. Kelly, Matthew R. Naylor, Hsiau-Wei Lee, Kayoko Kanamitsu, Mayumi Ishii, Ryosuke Ueki, Takumi Ueda, Koh Takeuchi, Masatake Sugita, Yutaka Akiyama, Scott R. Lokey, Jumpei Morimoto, Shinsuke Sando
Summary: Naturally occurring peptides with high membrane permeability usually have ester bonds on their backbones. This study evaluated the effect of amide-to-ester substitutions on the membrane permeability of cyclic peptides and found that this substitution is effective in improving membrane permeability. The findings provide insights into the development of membrane-permeable peptides through appropriate utilization of amide-to-ester substitutions.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Michiko Tajiri, Shunsuke Imai, Tsuyoshi Konuma, Keiko Shimamoto, Ichio Shimada, Satoko Akashi
Summary: We developed a platform using native mass spectrometry to investigate the responses of G-protein-coupled receptors (GPCRs) to agonists and antagonists. By utilizing mini-G(s) and nanobody80 (Nb80) that mimic the G & alpha; interface of GPCRs, we successfully observed the ligand-bound human & beta;(2) adrenergic receptor (h & beta;(2)AR). The ratio of h & beta;(2)AR-mini-G(s) or -Nb80 complexes observed in mass spectra showed a strong correlation with agonist/antagonist efficacy obtained from a cell-based assay.
Article
Multidisciplinary Sciences
Shunsuke Imai, Hiroshi Suzuki, Yoshinori Fujiyoshi, Ichio Shimada
Summary: This study analyzes the three-dimensional structure of the complex formed by the EMCV IRES, the HEAT1 domain fragment of eIF4G, and eIF4A using cryo-electron microscopy. Two eIF4G-interacting domains on the IRES are identified and the formation of the complex changes the angle between them. The dynamics of these domains are further explored using solution NMR spectroscopy, revealing conformational equilibria in the microsecond to millisecond timescale. This study provides insights into the viral RNA's sophisticated strategy for optimal docking to hijack the host protein.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Yugo Shimizu, Tomoki Yonezawa, Yu Bao, Junichi Sakamoto, Mariko Yokogawa, Toshio Furuya, Masanori Osawa, Kazuyoshi Ikeda
Summary: We improved the hit rate against a protein-protein interaction target by combining a library of medium-sized molecules with iterative screening using multiple ligand-based machine learning algorithms. Inhibition assays using a PPI target, Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2), demonstrated that a deep neural network model based on the first-round assay data achieved the highest hit rate of 27.3%. As a result of using these models, we identified novel active and non-flat compounds that were not present in public datasets, expanding the chemical space.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Yuko Tsuchiya, Tomoki Yonezawa, Yu Yamamori, Hiroko Inoura, Masanori Osawa, Kazuyoshi Ikeda, Kentaro Tomii
Summary: This article introduces the PoSSuM database, which can be used to identify similar binding pockets in proteins, and its drug search feature can investigate the diversity of ligands and receptors in these pockets. In addition, two new databases are introduced: PoSSuMAg for studying antibody-antigen interactions, and PoSSuMAF for simplifying the exploration of putative pockets in AlphaFold human protein models.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Organic
Jungyeon Kim, Hiroka Kobayashi, Marin Yokomine, Yota Shiratori, Takumi Ueda, Koh Takeuchi, Koji Umezawa, Daisuke Kuroda, Kouhei Tsumoto, Jumpei Morimoto, Shinsuke Sando
Summary: This study reports the first design strategy for beta-peptoids, in which all four backbone dihedral angles are rotationally restricted on a per-residue basis. The introduction of a cyclopentane constraint realized the preorganized monomer structure and led to a beta-peptoid with a stable twisted strand shape.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Abhinav Dubey, Thibault Viennet, Sandeep Chhabra, Koh Takeuchi, Hee-Chan Seo, Wolfgang Bermel, Dominique P. Frueh, Haribabu Arthanari
Summary: Intrinsically disordered regions (IDRs) of proteins play critical roles in the regulation of biological processes but are challenging to study structurally. This study improves the methodology of analyzing IDRs using nuclear magnetic resonance (NMR) by using transverse relaxation optimized spectroscopy (TROSY) at higher magnetic fields and physiological salt concentrations. The new methods have been successfully applied to assign large disordered regions with low sequence complexity.
CHEMICAL COMMUNICATIONS
(2022)
