Article
Chemistry, Multidisciplinary
Pokhraj Ghosh, Molly Stauffer, Valiallah Hosseininasab, Subrata Kundu, Jeffery A. Bertke, Thomas R. Cundari, Timothy H. Warren
Summary: Copper nitrite reductases convert nitrite ions to nitric oxide and nitrous oxide at high levels of nitrogen oxide flux. The assembly of nitric oxide at a single copper site to form copper cis-hyponitrites has been demonstrated in the presence of an external reductant. Furthermore, the removal of a fraction of the structure in the copper cis-hyponitrite complex can be achieved by adding specific reagents, resulting in the formation of a spectroscopically similar anion. These studies provide insights into the reductive coupling of nitrogen oxides at a single copper center and the utilization of the strong oxidizing power of nitrite.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Alex J. Flynn, Svetlana V. Antonyuk, Robert R. Eady, Stephen P. Muench, S. Samar Hasnain
Summary: The cryoEM structure of qNOR from Alcaligenes xylosoxidans provides insights into its crucial role in the denitrification pathway and sheds light on the mechanisms of electron, substrate, and proton transport.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Margareta R. A. Blomberg
Summary: Improvements in density functional theory methodology have made it a powerful tool in studying enzymatic reaction mechanisms, but concerns remain about the reliability of results for metalloenzymes. By using different DFT functionals and combining with experimental data, stable qualitative pictures of reaction mechanisms were obtained.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Zhanfeng Wang, Sason Shaik, Binju Wang
Summary: Cytochrome P450 monooxygenases (P450s) are versatile biocatalysts used in various fields, and recent research has revealed new insights into the long-range electron transfer mechanisms within the enzyme. The study utilized molecular dynamics simulations to uncover the interdomain electron transfer process between ferredoxin and heme, providing a clearer understanding of the catalytic cycle of P450s. Additionally, key residues involved in electron transfer pathways were identified, aiding in the development of more efficient biocatalysts in the future.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Tomas Rodriguez-Gil, Alejandro Torrado, Macarena Iniesta-Pallares, Consolacion alvarez, Vicente Mariscal, Fernando P. Molina-Heredia
Summary: Cytochrome c(M) was first described in 1994 and its sequence has been found in the genome of many cyanobacterial species. Recent research suggests that its 3D structure is similar to the C subunit of bacterial nitric oxide reductase, potentially locating it in the thylakoid membrane and giving it a new role.
APPLIED SCIENCES-BASEL
(2021)
Article
Biochemistry & Molecular Biology
Carmen M. Bellido-Pedraza, Victoria Calatrava, Angel Llamas, Emilio Fernandez, Emanuel Sanz-Luque, Aurora Galvan
Summary: In this study, we used mutants of nitrite reductase to investigate the rates and kinetics of N2O release and the metabolism of this greenhouse gas. Our results show that N2O production is influenced by light and requires nitrate reductase as the major provider of NO.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Sarah L. Schwartz, Lily Momper, Luiz Thiberio Rangel, Cara Magnabosco, Jan P. Amend, Gregory P. Fournier
Summary: Denitrification plays a central role in the global nitrogen cycle. The study reveals a greater diversity of denitrification enzyme arrangements than previously reported.
Article
Biochemistry & Molecular Biology
Rene F. Gorriz, Petra Imhof
Summary: Cytochrome c oxidase is a membrane protein that plays a crucial role in proton transport and oxidation reaction. Our molecular dynamics simulations reveal that the position of protons affects the number of water molecules in the channel. Higher hydration levels facilitate proton transfer. The bottom of the channel, E101, has minimal impact on proton transfer, but H96 acts as the initial proton acceptor.
Article
Biochemistry & Molecular Biology
Joanna A. Quaye, Giovanni Gadda
Summary: Pseudomonas aeruginosa uses D-2-hydroxyglutarate dehydrogenase (PaD2HGDH) to couple the oxidation of D-2-hydroxyglutarate (D2HG) to L-serine biosynthesis for survival. Knockout of PaD2HGDH hinders the growth of P. aeruginosa, making it a potential therapeutic target. This study investigates the metal composition and role of metal as an activator or cofactor for PaD2HGDH.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
John Ukeri, Michael T. Wilson, Brandon J. Reeder
Summary: Cytoglobin has physiological roles that are not clearly understood, but may include regulation of nitric oxide, oxygen sensing, and protection against oxidative stress. Specific mutations can affect the nitric oxide binding and metabolism activities of cytoglobin, helping to understand its precise role under physiological and pathophysiological conditions.
Article
Biochemistry & Molecular Biology
Arnab Ghosh, Cynthia J. Koziol-White, William F. Jester, Serpil C. Erzurum, Kewal Asosingh, Reynold A. Panettieri, Dennis J. Stuehr
Summary: The study revealed that severe asthmatics have inherent defects in sGC in their airway smooth muscle, leading to impaired NO-sGC-cGMP signaling. This dysfunction is associated with changes in cell redox enzymes that impact sGC maturation and function.
Article
Biochemistry & Molecular Biology
Natalia Napieraj, Malgorzata Janicka, Beata Augustyniak, Malgorzata Reda
Summary: This study reveals the important regulatory role of exogenous putrescine (Put) in nitric oxide (NO) production in cucumber roots under salt stress conditions. Put reduces NO levels in short-term salt stress, but increases NO levels in long-term salt stress. Additionally, Put modulates NO biosynthesis pathways and affects nitrate reductase (NR) activity to regulate salt stress response.
Article
Chemistry, Inorganic & Nuclear
Matthew R. Dent, Anthony W. DeMartino, Jesus Tejero, Mark T. Gladwin
Summary: Interdisciplinary research has revealed the essential roles of nitric oxide (NO) as a signaling molecule in various physiological pathways relevant to human health and disease. Hemeproteins, including hemoglobin and myoglobin, play central roles in generating and maintaining NO as well as serving as a stable reservoir for NO in the form of nitrite. These pathways involve complex chemical and biochemical reactions that govern NO and nitrite signaling in vivo, presenting potential therapeutic targets for treating a wide range of diseases.
INORGANIC CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Nolan T. Carew, Heidi M. Schmidt, Shuai Yuan, Joseph C. Galley, Robert Hall, Helene M. Altmann, Scott A. Hahn, Megan P. Miller, Katherine C. Wood, Bethann Gabris, Margaret C. Stapleton, Sean Hartwick, Marco Fazzari, Yijen L. Wu, Mohamed Trebak, Brett A. Kaufman, Charles F. McTiernan, Francisco J. Schopfer, Placido Navas, Patrick H. Thibodeau, Dennis M. McNamara, Guy Salama, Adam C. Straub
Summary: This study reveals the crucial role of cytochrome b5 reductase 3 (CYB5R3) in cardiomyocyte redox biology and identifies a common genetic variant that may increase the risk of death in Black patients with heart failure.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Cell Biology
A. T. Duarte-Silva, L. G. R. Ximenes, M. Guimaraes-Souza, I. Domith, R. Paes-de-Carvalho
Summary: The communication and interaction between developing neurons and neurotransmitters play crucial roles in the regulation of signaling pathways during central nervous system development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kiyoshi Yagi, Suyong Re, Takaharu Mori, Yuji Sugita
Summary: Recent advances in atomistic molecular dynamics simulations have allowed us to explore the conformational spaces of biomolecules and observe transitions between distinct structures. Weight average approaches are used to analyze various experimental measurements and improve our understanding of molecular functions based on atomic structures.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Cheng Tan, Jaewoon Jung, Chigusa Kobayashi, Diego Ugarte La Torre, Shoji Takada, Yuji Sugita
Summary: Residue-level coarse-grained (CG) models play a crucial role in biomolecular simulations, enabling the study of large-scale biological phenomena with unified treatments of proteins and nucleic acids, as well as efficient parallel computations. The toolbox and methods introduced can help optimize the performance in CG MD simulations.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biology
Hisham M. Dokainish, Suyong Re, Takaharu Mori, Chigusa Kobayashi, Jaewoon Jung, Yuji Sugita
Summary: The Spike protein plays a crucial role in neutralization and vaccine development for SARS-CoV-2. Its inherent flexibility provides essential information for designing antiviral drugs and vaccines.
Article
Chemistry, Medicinal
Hiraku Oshima, Yuji Sugita
Summary: The free-energy perturbation (FEP) method is an essential tool in in silico drug design, used to predict the free-energy changes of biomolecules in solvation and binding. However, conventional FEP requires computationally expensive reciprocal-space calculations. To address this limitation, this study proposes a modified Hamiltonian approach that introduces nonuniform scaling into the electrostatic potential, improving computational performance and avoiding the need for additional reciprocal-space calculations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Mao Oide, Yuji Sugita
Summary: In this study, a novel approach using the UMAP method was proposed to construct protein conformational landscapes, and native contact likelihood was used as feature variables to explore intermediate structures in protein folding. This method is useful for studying large-scale conformational changes in biomacromolecules.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Hiro Nakamura, Tamao Hisano, Md Mahfuzur Rahman, Takehiko Tosha, Mikako Shirouzu, Yoshitsugu Shiro
Summary: Bacterial pathogens use the ATP-binding cassette heme-dedicated efflux pump HrtBA to expel heme from the bacterial membranes to overcome cytotoxic effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biophysics
Hisham M. Dokainish, Yuji Sugita
Summary: A single mutation (D614G) in the spike protein of SARS-CoV-2, which causes COVID-19, has become the dominant variant. This mutation enhances the virus's infectivity by inducing structural changes. Molecular dynamics simulations reveal that the mutation orders the structure, weakens local interactions, and alters global interactions, leading to conformational changes. Understanding this mutation is crucial as it is present in all variants of concern.
BIOPHYSICAL JOURNAL
(2023)
Article
Chemistry, Physical
Hanae Takeda, Kanji Shimba, Masaki Horitani, Tetsunari Kimura, Minoru Kubo, Takashi Nomura, Takehiko Tosha, Yoshitsugu Shiro
Summary: This study demonstrates the trapping of short-lived reaction intermediates of metalloenzymes through the photolysis of a caged compound under cryogenic temperature followed by thermal annealing. This technique is essential for elucidating the mechanism of the reaction catalyzed by metalloenzymes.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Review
Biophysics
Yasuhiro Matsunaga, Motoshi Kamiya, Hiraku Oshima, Jaewoon Jung, Shingo Ito, Yuji Sugita
Summary: MBAR is a widely used method in analyzing MD simulation data to estimate free-energy changes between different states and averaged properties. Due to its broad applicability, the MBAR equations are rather difficult to apply for free-energy calculations using different types of MD simulations.
BIOPHYSICAL REVIEWS
(2022)
Article
Chemistry, Multidisciplinary
Jaewoon Jung, Chigusa Kobayashi, Yuji Sugita
Summary: gREST is an enhanced sampling algorithm used for proteins or other systems with rugged energy landscapes. It differs from the REMD method as the solvent temperatures are the same in all replicas, while solute temperatures are different and frequently exchanged between replicas to explore various solute structures. The gREST scheme is applied to large biological systems using a large number of processors, reducing communication time and performing energy evaluations on-the-fly during simulations. These advanced schemes in the GENESIS software provide new possibilities for studying large biomolecular complex systems with slow conformational dynamics.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Cheng Tan, Ai Niitsu, Yuji Sugita
Summary: In this study, the interactions between Hero11 protein and TDP-43-LCD protein were investigated using multiscale molecular dynamics simulations. Three possible regulatory mechanisms of Hero11 were proposed based on the simulation results. It was found that Hero11 can permeate into TDP-43-LCD condensates and induce changes in their conformation, intermolecular interactions, and dynamics. These mechanisms provide new insights into the regulation of biomolecular condensation under different conditions.
Article
Chemistry, Physical
Diego Ugarte La Torre, Shoji Takada, Yuji Sugita
Summary: iSoLF is a coarse-grained model used in molecular dynamics simulations of biological membranes with the implicit solvent approximation. By explicitly treating the electrostatic interactions and adding new particle types, the model can now simulate a wider range of lipid molecules. The improved model has been parameterized and validated, and it is also capable of simulating phase behaviors of lipid mixtures.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Hanae Takeda, Kanji Shimba, Masaki Horitani, Tetsunari Kimura, Takashi Nomura, Minoru Kubo, Yoshitsugu Shiro, Takehiko Tosha
Summary: The characterization of short-lived reaction intermediates is crucial for understanding the mechanism of metalloenzyme-catalyzed reactions. In this study, we demonstrated that the photolysis of a caged compound followed by thermal annealing is an effective technique for trapping short-lived reaction intermediates of metalloenzymes. By applying this technique to the study of membrane-integrated nitric oxide reductase (NOR), we were able to trap and characterize the intermediate species involved in the reductive coupling of NO molecules by NOR at its heme/nonheme FeB binuclear center.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Multidisciplinary
Isseki Yu, Takaharu Mori, Daisuke Matsuoka, Donatas Surblys, Yuji Sugita
Summary: The rapid increase in computational power has enabled atomistic molecular dynamics simulations of biomolecules in large-scale biological systems. Spatial decomposition analysis (SPANA) reduces computational time and memory size by distributing analysis tasks to multiple CPU cores, opening new possibilities for detailed atomistic analyses of biomacromolecules and other molecules in MD simulation trajectories.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Daiki Matsubara, Kento Kasahara, Hisham M. Dokainish, Hiraku Oshima, Yuji Sugita
Summary: Proper balance between protein-protein and protein-water interactions is crucial for molecular dynamics simulations of proteins. Increasing the protein-water interactions helps optimize the balance and has significant effects on diffusive properties of proteins in crowded solutions.