Article
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Thirupathi Ravula, Edgar M. Faison, Marco Tonelli, Qi Zhang, Ayyalusamy Ramamoorthy
Summary: In this study, polymer-based nanodiscs were used to measure RDCs from nucleic acids. The nanodiscs were characterized and their alignment stability was confirmed. RDCs from a labeled nucleic acid molecule were successfully measured using the aligned nanodiscs. This demonstrates the potential of SMA-EA-based lipid-nanodiscs for structural and dynamical studies of nucleic acids.
Article
Biochemistry & Molecular Biology
Giuliana Fusco, Francesco Bemporad, Fabrizio Chiti, Christopher M. M. Dobson, Alfonso De Simone
Summary: Understanding the differences in adaptation between proteins from hyperthermophilic organisms and their mesophilic homologues is crucial for unraveling the mechanisms of biological activity in proteins. Researchers measured NMR residual dipolar couplings and performed additional NMR experiments to study the structural and dynamical properties of a hyperthermophilic acylphosphatase enzyme and a human homologue. The results identified key differences in protein-protein and protein-ligand interactions, shedding light on the structure-dynamics-function relationship associated with the thermal adaptation strategies of protein molecules.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Max Hirschmann, Olaf Soltwedel, Philipp Ritzert, Regine von Klitzing, Christina M. Thiele
Summary: Two polyaspartates, PpFABLA (1) and co-polyaspartate PpFABLA-co-PBLA [11, 75% (n/n) PpFABLA content], bearing ortho-fluorinated azo-benzenes (pFAB) as photo-responsive groups, undergo reversible coil-helix transition in solution through the E/Z-isomerization of the side chain. The thermal stability of the Z-isomer is increased by pFAB, and the helix formation is effectively prevented. The helical polymer forms a lyotropic liquid crystal (LLC) and orients unidirectionally inside a magnetic field, while the coil polymer results in an isotropic solution.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Max Hirschmann, Olaf Soltwedel, Philipp Ritzert, Regine von Klitzing, Christina M. Thiele
Summary: Two polyaspartates with ortho-fluorinated azo-benzenes (pFAB) as photo-responsive groups in the side chain were synthesized: PpFABLA (1) and co-polyaspartate PpFABLA-co-PBLA [11, 75%(n/n) PpFABLA content]. PpFABLA (1) undergoes a visible-light-induced reversible coil-helix transition in solution due to the E/Z-isomerization of the side chain. PpFABLA-co-PBLA (11) forms a helix independently of the E/Z-isomerization of the side chain and exhibits changes in the morphology and dipolar coupling.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Polymer Science
Timo Imhof, Jonas Kind, Christina M. Thiele
Summary: We studied the temperature-dependent LLC behavior of helically chiral polypeptides, specifically PBPMLG and PBLA-co-PPLA. We observed a characteristic jump in the quadrupolar splittings Delta nu Q of the solvent's 2H signal during the transition of polymer rods from perpendicular to parallel orientation with respect to the magnetic field. By correlating Delta nu Q with the diffusion coefficients measured parallelly (D parallel to) and perpendicularly (D perpendicular to) to the magnetic field, we found a significant change in the D parallel to/D perpendicular to ratio at the transition temperature of the LLC phases.
Article
Chemistry, Multidisciplinary
Michael Reggelin, Stefan Immel
Summary: The study investigates the impact of vibrational analysis on the accuracy of back-calculating RDCs from molecular models, and the effects of thermal motions on the differentiability of diastereomers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Multidisciplinary
Francois-Xavier Theillet
Summary: In-cell structural biology by NMR spectroscopy aims to extract structural information of proteins or nucleic acids in their native cellular environments. This review provides comprehensive but accessible information on the methods, fundamental knowledge, and applications of in-cell structural biology by NMR, along with an overview of other related techniques. In the era of large-scale screenings and deep learning, NMR spectroscopy plays a vital role in providing accurate and qualitative experimental evidence to understand the cellular interior.
Review
Chemistry, Multidisciplinary
Francois-Xavier Theillet
Summary: In-cell structural biology by NMR aims to extract structural information about proteins or nucleic acids in their natural cell environment. NMR spectroscopy plays a crucial role in providing accurate and quantitative experimental evidence for understanding the interior life of cells.
Article
Chemistry, Multidisciplinary
Sirine Nouri, Julien Boudet, Hiang Dreher-Teo, Frederic H. -T. Allain, Rudi Glockshuber, Loic Salmon, Christoph Giese
Summary: In NMR spectroscopy, residual dipolar couplings (RDCs) are highly accurate probes for investigating biological structure and dynamics. Type 1 pili, derived from bacteria, are introduced as an alternative liquid-crystalline alignment medium for measuring RDCs. By elongating wild-type pili, the medium is made suitable for efficient NMR sample preparation. Additionally, type 1 pili demonstrate compatibility with challenging experimental conditions, making them a valuable alternative to traditional alignment media in NMR studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Niels Karschin, Stefan Becker, Christian Griesinger
Summary: This study presents a new approach using pseudocontact shifts and residual dipolar couplings to study protein interdomain motion. By sampling the conformational space and using a genetic algorithm, an accurate and reproducible model of the interdomain motion of Calmodulin/Munc13-1 was obtained without prior knowledge from crystallography.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Luca Venturi, Emanuela Bua, Giulia Caputo, Valentina Mileo
Summary: Residual dipolar couplings (RDCs) are a powerful tool in nuclear magnetic resonance (NMR) analysis for determining the structure of organic molecules. They are particularly valuable in the pharmaceutical industry for characterizing the stereochemistry of new chemical entities (NCEs) during the drug development process. In our study, RDCs were used to study the conformation and configuration of synthetic steroids with multiple stereocenters. We successfully identified the correct relative configuration for both prednisone and beclomethasone dipropionate (BDP), despite the large number of possible diastereoisomers.
Review
Biochemistry & Molecular Biology
Julia Koehler Leman, Georg Kuenze
Summary: Nuclear magnetic resonance (NMR) spectroscopy allows for the study of protein structures and dynamics. Although it can be challenging to collect sufficient NMR data for complex proteins, computational modeling techniques, such as those provided by the Rosetta software, can supplement sparse data and improve structure determination. This review provides an overview of the computational protocols in Rosetta for modeling protein structures from NMR data, including new developments for paramagnetic NMR, hydrogen-deuterium exchange, and chemical shifts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Martin D. Gelenter, Ad Bax
Summary: Post-translational modifications are commonly found in eukaryotic proteomes. However, these modifications are rarely studied using NMR in eukaryotic proteins, which are usually produced in E. coli through recombinant expression. The native C-terminal amide of melittin, a major peptide in honey bee venom, significantly affects its structure and dynamics. This study presents a method to produce isotopically labeled native melittin through recombinant expression and chemical amidation. It also confirms the accuracy of structural models generated by AlphaFold-Multimer using experimental residual dipolar couplings.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Daiane S. Carvalho, Danilo G. B. da Silva, Fernando Hallwass, Armando Navarro-Vazquez
Summary: An NMR weakly-aligning polymer gel was prepared by copolymerization of acrylonitrile and 2-acrylamide-2-methyl-1-propanesulfonic acid with 1,4-butanediol diacrylate as a cross-linker. The gel swells in water over a wide range of temperatures, but its swelling ratio is reduced in saline solutions. The gel can undergo reversible mechanical compression, generating anisotropy, which is easily observed in H-2 NMR experiments and allows for measurement of D-1(CH) residual dipolar couplings (RDCs) through F1-coupled HSQC experiments. The gel's performance as an NMR alignment medium was evaluated for various water-soluble organic molecules, providing proper-sized RDCs for sucrose and even small molecules such as 5-norbornen-2-ol, but strong interaction between the gel and molecules like azidothymidine and cefuroxime sodium salt prevented successful extraction of RDCs.
Article
Multidisciplinary Sciences
Kulkarni Madhurima, Bodhisatwa Nandi, Sneha Munshi, Athi N. Naganathan, Ashok Sekhar
Summary: The structure of a thermally accessible excited state in equilibrium with the native ensemble of a bacterial transcriptional regulator CytR has been determined using multinuclear CEST NMR. Evidence from double resonance CEST experiments suggests that the excited state, which resembles the DNA-bound form of CytR, recognizes DNA through a folding-before-binding conformational selection pathway. The disorder-to-order regulatory switch in DNA recognition by natively disordered CytR operates through a dynamical variant of the lock-and-key mechanism.
Article
Biochemistry & Molecular Biology
Giacomo Parigi, Enrico Ravera, Claudio Luchinat
Summary: Paramagnetic effects in NMR spectra provide valuable information on structure, electronic properties, and dynamics in biological systems. These effects are used for protein structure determination, refinement, and analysis of domain arrangement. Recent advances in quantum chemistry treatment enable high-resolution refinement of protein structures at metal coordination sites.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Meteorology & Atmospheric Sciences
L. Warwick, H. Brindley, A. Di Roma, S. Fox, S. Havemann, J. Murray, H. Oetjen, H. C. Price, D. Schuttemeyer, L. Sgheri, D. A. Tiddeman
Summary: This study investigates the retrieval of mid and upper tropospheric water vapor concentrations using airborne observations of far-infrared radiances. The results show that utilizing far-infrared measurements improves water vapor retrievals compared to in situ measurements, especially in the mid-upper troposphere. The performance of mid-infrared radiances is much reduced, while the advantage of far-infrared measurements is maintained even when the spectral resolution is reduced.
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES
(2022)
Article
Biochemical Research Methods
Giulia Licciardi, Domenico Rizzo, Maria Salobehaj, Lara Massai, Andrea Geri, Luigi Messori, Enrico Ravera, Marco Fragai, Giacomo Parigi
Summary: Biologics, as an important class of drugs, show great potential in treating various diseases. In this study, a gadolinium(III)-DOTA derivative was conjugated with asparaginase to evaluate its effectiveness as a theranostic agent. The results indicate that this protein complex exhibits significantly higher relaxivity, suggesting its potential use as an MRI contrast agent.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Linda Cerofolini, Kiefer O. Ramberg, Luis C. Padilla, Pawel Antonik, Enrico Ravera, Claudio Luchinat, Marco Fragai, Peter B. Crowley
Summary: Protein frameworks are emerging biomaterials with potential medical and technological applications. This study introduces a complementary strategy using solid-state NMR analysis to characterize low-crystallinity frameworks, specifically focusing on a microcrystalline protein-macrocycle framework and its rehydrated freeze-dried form.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Andrea Brunetti, Angela Pintus, Lorenzo Lombardi, Alessandro Kovtun, Federico Mascietti, Francesco Bruno, Enrico Ravera, Manuela Melucci, Giulio Bertuzzi, Marco Bandini
Summary: The chemodivergent ring-opening of cyclobutanols is facilitated by graphene oxide (GO) as a carbocatalyst. The amount of GO used in the reaction determines the synthesis of diverse functionalized dienes or indenes (26 examples). Spectroscopic (XPS and ssNMR) and experimental investigations reveal the direct involvement of GO's p-domains in regulating the stability of carbocationic intermediates during the reaction.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Margherita Verrucchi, Gina Elena Giacomazzo, Patrick Severin Sfragano, Serena Laschi, Luca Conti, Marco Pagliai, Cristina Gellini, Marilena Ricci, Enrico Ravera, Barbara Valtancoli, Claudia Giorgi, Ilaria Palchetti
Summary: A water-soluble ruthenium(II) complex (L) was used to modify the surface of an indium-tin oxide (ITO) electrode decorated with a nanostructured layer of TiO2 (TiO2/ITO). Singlet oxygen (O-1(2)) produced by the complex under visible light irradiation triggers a cathodic photocurrent when the electrode is illuminated and biased at a proper reduction potential. The L/TiO2/ITO electrode was characterized and demonstrated efficient oxidation of phenolic compounds, with a limit of detection (LOD) of 0.3 mu mol dm(-3).
Article
Nanoscience & Nanotechnology
Megan A. Kaster, Mikail D. Levasseur, Thomas G. W. Edwardson, Michael A. Caldwell, Daniela Hofmann, Giulia Licciardi, Giacomo Parigi, Claudio Luchinat, Donald Hilvert, Thomas J. Meade
Summary: Diagnostic medical imaging uses magnetic resonance (MR) to provide comprehensive information in a single scan. This study examined the MR performance of Gd(III)-labeled cages, AaLS-13 and OP, and found that they significantly enhanced proton relaxivity compared to the Gd(III) complex alone. The enhanced relaxivity was attributed to the slow molecular tumbling and restricted local motion of the conjugated Gd(III) complex.
ACS APPLIED BIO MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Giacomo Parigi, Enrico Ravera, Mario Piccioli, Claudio Luchinat
Summary: Mobility is a crucial feature for the function of biomacromolecules, leading to a conformational ensemble rather than a single conformation. NMR paramagnetic data, especially when combined with other data sources, provide valuable information to monitor the conformational variability. By virtue of their long-range nature, paramagnetic data can demonstrate conformational rearrangements, reveal minor conformational states, indicate representative conformations, and provide upper limits for each conformation's weight.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jian-Hong Tang, Hao Li, Chaonan Yuan, Giacomo Parigi, Claudio Luchinat, Thomas J. Meade
Summary: We have developed a new enzyme-activatable agent for real-time detection of bio-events in whole animals using magnetic resonance imaging. This new agent has a low magnetic resonance relaxivity in the off-state but generates significantly higher relaxivity upon enzymatic processing. Mechanistic insights regarding the magnetic resonance signal enhancement at the molecular scale were obtained through single X-ray crystal and nuclear magnetic relaxation dispersion analyses.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Francesco Bruno, Letizia Fiorucci, Enrico Ravera
Summary: When dealing with samples that have poor signal-to-noise ratio, it is often necessary to choose between taking a few points with a large number of scans to maximize signal-to-noise ratio or more points with a smaller number of scans to maximize information content. In this study, we demonstrate how low-rank decomposition can be utilized to denoise a series of spectra, reducing the trade-off between the number of scans and the number of experiments.
MAGNETIC RESONANCE IN CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Fabio Carniato, Marco Ricci, Lorenzo Tei, Francesca Garello, Chiara Furlan, Enzo Terreno, Enrico Ravera, Giacomo Parigi, Claudio Luchinat, Mauro Botta
Summary: This article describes nanogels based on a chitosan matrix stabilized by a Mn-t-CDTA bisamide derivative. These nanogels are proposed as an alternative to less stable paramagnetic nanogels obtained by electrostatic interactions. The novel nanogels have improved relaxivity values, high stability, good extravasation and accumulation, and high T-1 contrast in tumors. These properties make them promising MRI probes for in vitro and in vivo preclinical applications.
Article
Biochemistry & Molecular Biology
Francesca Di Cesare, Alessia Vignoli, Claudio Luchinat, Leonardo Tenori, Edoardo Saccenti
Summary: This study analyzed the association networks of serum metabolites and found that the metabolite-metabolite association network of colorectal cancer (CRC) patients is distinct from that of patients with polyposis and healthy controls. Energy metabolism-related nodes play a crucial role in the CRC network.
Article
Chemistry, Multidisciplinary
Francielli S. Santana, Mauro Perfetti, Matteo Briganti, Francesca Sacco, Giordano Poneti, Enrico Ravera, Jaisa F. Soares, Roberta Sessoli
Summary: The article presents a dysprosium complex that is chemically designed to exhibit strong easy-axis type magnetic anisotropy preserved in dichloromethane solution at room temperature. The detailed theoretical and experimental studies explain the typical features of highly performant single molecule magnets (SMMs). The NMR characterization shows remarkably large chemical shifts, outperforming the current state-of-the-art pseudocontact shift (PCS) tags.
