Article
Chemistry, Multidisciplinary
Sinead McCann, William E. Roe, Hannah E. Agnew, Peter C. Knipe
Summary: To imitate the dynamic molecules in biological systems, foldamers need to possess stimulus-responsive behavior. In this study, we present a foldamer architecture based on alternating pyridine-diketopiperazine linkers. Epimerization is prevented via a copper-catalyzed coupling protocol. The native conformation of the compounds is initially investigated in both solid and solution states. The foldamers can be solubilized in DMSO and pH 9.5 buffer while retaining conformational control. Furthermore, dynamic switching is demonstrated through acid treatment, resulting in stimulus-responsive sidechain reconfiguration.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
P. P. Kobchikova, S. Efimov, I. A. Khodov, V. V. Klochkov
Summary: In this study, cyclosporins D, E, and G were characterized by NMR spectroscopy and molecular dynamics simulation to investigate their structure features and backbone flexibility. It was found that these peptides share common characteristics, with the exception of CsE, which lacks backbone dynamics at the nanosecond timescale, raising questions about its biological activity.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Physical
Kris Strunge, Tucker Burgin, Thaddeus W. Golbek, Steven J. Roeters, Jim Pfaendtner, Tobias Weidner
Summary: α-synuclein folds into a defined secondary structure at the air-water interface, promoting its aggregation and fibrillation. Understanding the role of hydrophobic surfaces in this process is important for studying severe brain disorders such as Parkinson's disease.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Alida Besch, William M. Marsiglia, Moosa Mohammadi, Yingkai Zhang, Nathaniel J. Traaseth
Summary: Many human cancers are treated with small molecule inhibitors that target the kinase domain of receptor tyrosine kinases. Long-term treatment often leads to drug resistance mutations at the gatekeeper residue, increasing the aggressiveness of the cancer. However, the mechanism of gain-of-function by gatekeeper mutations is poorly understood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Applied
Adele Vanacore, Maria Concetta Forgione, Domenico Cavasso, Ha Ngoc Anh Nguyen, Antonio Molinaro, James P. Saenz, Gerardino D'Errico, Luigi Paduano, Roberta Marchetti, Alba Silipo
Summary: Methylobacterium extorquens strain PA1 secretes a diverse mixture of exopolysaccharides (EPSs), which may contribute to increased methanol tolerance and cell stability.
CARBOHYDRATE POLYMERS
(2022)
Article
Chemistry, Applied
O. N. Makshakova, E. R. Safarova, Y. F. Zuev
Summary: This study investigated the molecular interactions between RNase and polysaccharides, revealing the impact of polysaccharide side chains on protein structure in complexes. Computational simulations and spectroscopic analyses confirmed stable interactions, with potential implications for using rhamnogalacturonan I as a matrix material for protein delivery systems.
CARBOHYDRATE POLYMERS
(2021)
Article
Biochemistry & Molecular Biology
Carlos A. Elena-Real, Annika Urbanek, Lionel Imbert, Anna Morato, Aurelie Fournet, Frederic Allemand, Nathalie Sibille, Jerome Boisbouvier, Pau Bernado
Summary: A strategy for efficiently assigning frequencies to individual nuclei in large biomolecular machines and repetitive proteins using in vitro protein expression is presented. The approach was demonstrated to be applicable for NMR assignment in four proteins by introducing isotopically labeled alanines. The labeling method enabled unambiguous assignments in large protein assemblies and revealed the correlation between helical stability and homorepeat length in Phox2B. Selectively introducing alanines with distinct labeling patterns proves to be a powerful tool for studying challenging biomolecular systems.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Federica Maschietto, Erik Zavala, Brandon Allen, J. Patrick Loria, Victor Batista
Summary: In this study, computational modeling and solution NMR spectroscopy were combined to identify an allosteric site in MptpA. The findings suggest that this site plays a crucial role in substrate binding and reaction kinetics.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Physical
Yi Ji, Zhengmao Liu, Zhenchao Zhao, Pan Gao, Xinhe Bao, Kuizhi Chen, Guangjin Hou
Summary: The study investigates the molecular dynamics of molecules in MFI zeolites and finds that the structural differences have a significant impact on shape selectivity. In the absence of acid sites, molecules can only diffuse along straight channels and tend to occupy channel intersections. Different types of pore confinements result in different dynamic motions of the molecules. With the presence of acid sites, molecules are strongly adsorbed and their motions are further impeded.
Article
Chemistry, Medicinal
Yoseph Atilaw, Vasanthanathan Poongavanam, Caroline Svensson Nilsson, Duy Nguyen, Anja Giese, Daniel Meibom, Mate Erdelyi, Jan Kihlberg
Summary: PROTACs induce intracellular degradation of target proteins through a bifunctional structure. Structural insights into a VHL-based PROTAC revealed elongated and polar conformations in solutions, suggesting the importance of molecular chameleonicity for cell permeability.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Bruno Linclau, Zhong Wang, Benjamin Jeffries, Jerome Graton, Rodrigo J. Carbajo, Davy Sinnaeve, Jean-Yves Le Questel, James S. Scott, Elisabetta Chiarparin
Summary: Efficient drug discovery relies on optimizing bioactivity and compound properties such as lipophilicity, guided by efficiency metrics; the use of conformer-specific lipophilicities is a less explored strategy; optimizing lipophilicity values for different conformers can create a novel avenue in drug discovery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Polymer Science
Yiqing Wang, Xiao Tan, Adil Usman, Yuhao Zhang, Michal Sawczyk, Petr Kral, Cheng Zhang, Andrew K. Whittaker
Summary: A major challenge in the preparation of polymeric F-19 MRI contrast agents is signal attenuation caused by reduced segmental mobility of partly fluorinated polymers. This study focuses on the role of hydrophilic segments in imaging performance and explores the effect of different hydrophilic segments on F-19 imaging. The results highlight the importance of maintaining high fluorine visibility and long T-2 relaxation time for effective CAs.
Article
Chemistry, Multidisciplinary
Shun Dekura, Motohiro Mizuno, Hatsumi Mori
Summary: A salt with a three-dimensional hydrogen-bonded phosphate network and imidazolium cations was found to exhibit isotropic anhydrous superprotonic conductivity exceeding 10(-3) S cm(-1), which is achieved through the accelerated molecular motion along the proton conduction pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Albert A. Smith, Emelyne M. Pacull, Sabrina Stecher, Peter W. Hildebrand, Alexander Vogel, Daniel Huster
Summary: G protein-coupled receptors initiate signal transduction by binding with ligands. In this study, we focus on the growth hormone secretagogue receptor (GHSR), which binds with the 28 residue peptide ghrelin. We compared the dynamics of apo and ghrelin-bound GHSR using long molecular dynamics simulation trajectories and identified differences in dynamics in specific regions. We also investigated the traversal of GHSR over a rugged energy landscape via principal component analysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Mayra Queme-Pena, Tunde Juhasz, Gergely Kohut, Maria Ricci, Priyanka Singh, Imola Cs Szigyarto, Zita Papp, Livia Fulop, Tamas Beke-Somfai
Summary: Anticancer peptides have advantages targeting cell membranes, with three distinct binding modes identified: surface helical structure, partially helical structure with disordered regions, and non-inserted helical monomeric form.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Ya Gao, Jumin Lee, Iain Peter Shand Smith, Hwayoung Lee, Seonghoon Kim, Yifei Qi, Jeffery B. Klauda, Goran Widmalm, Syma Khalid, Wonpil Im
Summary: Hydrogen mass repartitioning allows for longer time steps in molecular dynamics simulations, improving conformational sampling in protein and phospholipid bilayers. CHARMM-GUI now supports diverse simulation programs and different protonation states for phosphate groups in lipopolysaccharides. The reliability of HMR in complex biomolecules like LPS is demonstrated through consistent conformational sampling, while different phosphate protonation states have slight impacts on lipid packing and properties.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Plant Sciences
Erwan Chavonet, Matthieu Gaucher, Romain Warneys, Antoine Bodelot, Christelle Heintz, Anthony Juillard, Raphael Cournol, Goran Widmalm, Joanna K. Bowen, Cyril Hamiaux, Marie-Noelle Brisset, Alexandre Degrave
Summary: This study identifies and characterizes a class of apple PR proteins called MdAGGs, which are abundantly produced in leaf tissues and correspond to enhanced resistance to E. amylovora. The study also reveals that E. amylovora represses the expression of MdAGG genes by injecting an effector and secreting bacterial exopolysaccharides. Furthermore, the study demonstrates that MdAGG protein can agglutinate E. amylovora cells and bind bacterial lipopolysaccharides in vitro.
Article
Chemistry, Medicinal
Federico Riu, Alessandro Ruda, Olof Engstrom, Claudio Muheim, Hani Mobarak, Jonas Stahle, Paul Kosma, Antonio Carta, Daniel O. Daley, Goran Widmalm
Summary: In this study, docking and molecular dynamics simulations were used to identify potential compounds from libraries A and B that can bind to WaaG. The substructure of the inner core of LPS was also investigated. The findings provide insights into the function and catalytic cycle of the enzyme WaaG.
Article
Biochemistry & Molecular Biology
Axel Furevi, Alessandro Ruda, Thibault Angles D'Ortoli, Hani Mobarak, Jonas Stahle, Christoffer Hamark, Carolina Fontana, Olof Engstrom, Patricia Apostolica, Goran Widmalm
Summary: This article introduces a method for determining the structure of carbohydrates using NMR spectroscopy and computational approaches. The CASPER program can predict H-1 and C-13 NMR chemical shifts based on chemical shift data, and the accuracy of these predictions can be improved by experimental assignment of chemical shifts. The program was used to predict chemical shifts and determine structures of oligosaccharides containing sialic acid and O-antigen polysaccharides from E. coli O174, showing good agreement between experimental and predicted data.
CARBOHYDRATE RESEARCH
(2022)
Review
Chemistry, Medicinal
Federico Riu, Alessandro Ruda, Roberta Ibba, Simona Sestito, Ilenia Lupinu, Sandra Piras, Goran Widmalm, Antonio Carta
Summary: This article introduces the differences between gram-positive and gram-negative bacteria, discusses the structural and functional properties of cell wall polysaccharides and peptidoglycan, and explores drug treatments targeting these structures and bacterial resistance to drugs. Additionally, the use of carbohydrate-based vaccines as a preventive strategy against bacterial infections is proposed.
Article
Chemistry, Multidisciplinary
Dirk Auman, Felix Ecker, Sophie L. Mader, Kevin M. Dorst, Alois Braeuer, Goran Widmalm, Michael Groll, Ville R. I. Kaila
Summary: In this study, we combine high-resolution X-ray crystallography, enzyme engineering, quantum-classical (QM/MM) simulations, and biochemical assays to uncover the existence of a peroxidic intermediate bridging the substrate and active site metal ion in AsqJ. We also find that the homolytic cleavage of this intermediate during substrate epoxidation generates an activated high-valent ferryl (FeIV = O) species for mediating the next catalytic cycle. These combined findings provide important insights into the chemical bond activation principles and molecular mechanisms of dioxygenases in complex enzymatic reaction networks.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Chemistry, Multidisciplinary
Carolina Fontana, Goran Widmalm
Summary: Glycans are important in biology and their structures, which determine their interaction with other molecules, can be resolved in greater detail using advanced NMR techniques and hardware developments.
Article
Chemistry, Medicinal
Ya Gao, Goran Widmalm, Wonpil Im
Summary: In this study, the impact of different forms of Escherichia coli extracellular capsule on the properties of LPS bilayers was investigated through molecular dynamics simulations. It was found that the presence of KLPS made the acyl chains of LPS more rigid and ordered, while the presence of KPG made them less ordered and flexible. These findings contribute to a better understanding of the biological functions of bacterial extracellular capsules and the properties of outer membranes.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Jeahoo Kwon, Alessandro Ruda, Hugo F. Azurmendi, Jasmin Zarb, Marcos D. Battistel, Liang Liao, Ari Asnani, France-Isabelle Auzanneau, Goran Widmalm, Daron I. Freedberg
Summary: We provide evidence for nonconventional hydrogen bonding in 10 Lewis antigens and two rhamnose analogues. The thermodynamics and kinetics of these hydrogen bonds are characterized, and a plausible explanation for their presence in Lewis antigens is presented. Our findings shed light on the contribution of nonconventional hydrogen bonding to molecular structure and can be used for rational drug design.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biology
Benjamin Wiseman, Goeran Widmalm, Martin Hoegbom
Summary: Through cryo-electron microscopy, it was discovered that the co-polymerase WzzE, responsible for length modulation of the enterobacterial common antigen, consists of eight subunits arranged in alternating up-down conformations. The clashing helical faces between adjacent protomers contribute to the alternating arrangement of the L4 loops, creating a dynamic environment for polysaccharide elongation. This study provides insight into the mechanisms of lipopolysaccharide elongation and length regulation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Organic
Marshall J. J. Smith, Emma L. L. Gates, Goran Widmalm, Ralph W. W. Adams, Gareth A. A. Morris, Mathias Nilsson
Summary: Human milk oligosaccharides are bioactive molecules that have diverse effects on infant development. NMR provides important structural information about these oligosaccharides, but signal overlap in the spectra makes this information difficult to obtain. This study demonstrates the benefits of combining pure shift methods with the CASPER computational approach for resonance assignment in oligosaccharides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Axel Furevi, Jonas Stahle, Claudio Muheim, Spyridon Gkotzis, Daniel O. Daley, Klas Udekwu, Goran Widmalm
Summary: The structure of the O-antigen from the international reference strain Escherichia coli O93:-:H16 has been determined using bioinformatics information, NMR spectra, and computer program CASPER. The polysaccharide carries O-acetyl groups, with varying locations on the repeating unit. The tetrasaccharide repeating unit of the O-antigen is similar to capsular polysaccharides from other E. coli strains.
Article
Chemistry, Medicinal
Ya Gao, Goran Widmalm, Wonpil Im
Summary: Capsule is a common virulence factor in Gram-negative bacteria, providing protection to pathogens from host defenses. This study models representative Escherichia coli CPS and incorporates it into symmetric bilayers with LPS. Molecular dynamics simulations reveal that the presence of CPS affects various properties of the bilayers, such as the rigidity and order of LPS's acyl chains.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Axel Furevi, Klas Udekwu, Goran Widmalm
Summary: This study elucidates the structure of the O-antigen polysaccharide from Enteropathogenic Escherichia coli O125ac:H6 through NMR experiments and sugar analysis, confirming a branched pentasaccharide structure for the repeating unit. Additionally, by utilizing the CASPER program, the O-antigen structure of O125ab, composed of hexasaccharide repeating units, was established in a semi-automated manner. The close similarity between the O-antigen structures supports the presence of two subgroups within the E. coli O125 serogroup.
Article
Chemistry, Multidisciplinary
Jin-Min Shi, Ting-Ting Wu, Hui Zhou, Yao-Yao Zhang, Li Liu, Goran Widmalm, Josef Voglmeir
Summary: Galactokinases (GalKs) are a group of structurally conserved proteins found in all life forms. A unique GalK orthologue from the bacterium Solitalea canadensis (ScGalK) has been discovered with relaxed substrate requirements and the ability to convert xylose to xylose-1-phosphate. Further investigation identified a putative Glucose-1-phosphate Uridyltransferase (ScGPUT) in close proximity to the ScGalK gene, which can convert xylose-1-phosphate to uridine diphosphate xylose (UDP-xylose) with the presence of uridine triphosphate (UTP).