A5039803640- Advanced NMR Techniques and Applications
- Photoreceptor and optogenetics research
- DNA and Nucleic Acid Chemistry
- Receptor Mechanisms and Signaling
- Solid-state spectroscopy and crystallography
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Amyotrophic Lateral Sclerosis Research
- Supramolecular Self-Assembly in Materials
- Protein Structure and Dynamics
- Retinal Development and Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- biodegradable polymer synthesis and properties
- Enzyme Structure and Function
- NMR spectroscopy and applications
- Peptidase Inhibition and Analysis
- Alzheimer's disease research and treatments
- Spectroscopy and Quantum Chemical Studies
- Chemical Synthesis and Analysis
- Advanced Electron Microscopy Techniques and Applications
- Thermal Radiation and Cooling Technologies
- Muon and positron interactions and applications
- Image Enhancement Techniques
- Social Media in Health Education
- Thermal properties of materials
Beijing National Laboratory for Molecular Sciences
2024-2025
Goethe University Frankfurt
2013-2024
Institute of Chemistry
2024
Chinese Academy of Sciences
2024
Shanghai Polytechnic University
2018
UCLA Health
2017
University of Florence
2010-2014
Interuniversity Consortium for Magnetic Resonance
2010-2014
Fondazione Farmacogenomica FiorGen
2011-2013
Chongqing University
2012
The amyloid fibrils of beta-amyloid (Aβ) peptides play important roles in the pathology Alzheimer's disease. Comprehensive solid-state NMR (SSNMR) structural studies on uniformly isotope-labeled Aβ assemblies have been hampered for a long time by sample heterogeneity and low spectral resolution. In this work, SSNMR well-ordered fibril samples Aβ40 with an additional N-terminal methionine provide high-resolution spectra which lead to accurate model. studied here carry distinct features...
G protein-coupled receptors (GPCRs) constitute a functionally diverse protein family and are targets for broad spectrum of pharmaceuticals. Technological progress in X-ray crystallography cryogenic electron microscopy has enabled extensive, high-resolution structural characterisation GPCRs different conformational states. However, as highly dynamic events underlie GPCR signalling, complete understanding functionality requires insights into their dynamics. Here, we present large dataset...
We show here that by combining tailored approaches based on ultrafast (60 kHz) MAS the CoII-replaced catalytic domain of matrix metalloproteinase 12 (CoMMP-12) we can observe and assign, in a highly paramagnetic protein solid state, 13C even 1H resonances from residues coordinating metal center. In addition, exploiting enhanced relaxation caused center, low power irradiation enabled fast MAS, this be achieved remarkably short times at very high field (21.2 T), with only less than 1 mg...
The combination of a red light PDT agent and Pt(II)-based chemotherapeutic drug at the molecular level maintains intrinsic functions each unit; conjugated complexes exhibit remarkable photocytoxicity demonstrate potential to serve as agents for DNA-targeting well photochemotherapy.
cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form a dissociation constant of 37 ± 3 μM through binding cysteine 111 (Cys111) located at edge subunit interface. It also binds Cu2–Zn2 and Zn2–Zn2 forms hSOD1. Cisplatin inhibits aggregation demetalated hSOD1, it further dissolve monomerize hSOD1 oligomers vitro cell, thus indicating its potential as leading compound for amyotrophic lateral sclerosis.
Abstract G protein‐coupled receptors (GPCRs) are one of the major drug targets. In recent years, computational design for GPCRs has mainly focused on static structures obtained through X‐ray crystallography, cryogenic electron microscopy (cryo‐EM) or in silico modelling as a starting point virtual screening campaigns. However, highly flexible entities with ability to adopt different conformational states that elicit physiological responses. Including this knowledge discovery pipeline can...
Proteorhodopsins are widely distributed photoreceptors from marine bacteria. Their discovery revealed a high degree of evolutionary adaptation to ambient light, resulting in blue- and green-absorbing variants that correlate with conserved glutamine/leucine at position 105. On the basis an integrated approach combining sensitivity-enhanced solid-state nuclear magnetic resonance (ssNMR) spectroscopy linear-scaling quantum mechanics/molecular mechanics (QM/MM) methods, this single residue is...
Proteorhodopsins (PRs) found in marine microbes are the most abundant retinal-based photoreceptors on this planet. PR variants show high levels of environmental adaptation, as their colors tuned to optimal wavelength available light. The two major green and blue subfamilies can be interconverted through a L/Q point mutation at position 105. Here we reveal structural basis behind intriguing color-tuning effect. High-field solid-state NMR spectroscopy was used visualize changes within directly...
Abstract Understanding the conformational sampling of translation-arrested ribosome nascent chain complexes is key to understand co-translational folding. Up now, coupling cysteine oxidation, disulfide bond formation and structure in chains has remained elusive. Here, we investigate eye-lens protein γB-crystallin ribosomal exit tunnel. Using mass spectrometry, theoretical simulations, dynamic nuclear polarization-enhanced solid-state magnetic resonance cryo-electron microscopy, show that...
Abstract Nuclear magnetic resonance (NMR) spectroscopy is a powerful and popular technique for probing the molecular structures, dynamics chemical properties. However conventional NMR bottlenecked by its low sensitivity. Dynamic nuclear polarization (DNP) boosts sensitivity orders of magnitude resolves this limitation. In liquid-state revolutionizing has been restricted to few specific non-biological model molecules in organic solvents. Here we show that carbon small biological molecules,...
The human transporter associated with antigen processing (TAP) is a 150 kDa heterodimeric ABC transport complex that selects peptides for export into the endoplasmic reticulum and subsequent loading onto major histocompatibility class I molecules to trigger adaptive immune responses against virally or malignantly transformed cells. To date, no atomic-resolution information on peptide–TAP interactions has been obtained, hampering mechanistic understanding of early steps substrate...
Abstract The accumulation of soluble toxic beta‐amyloid (Aβ) aggregates is an attractive hypothesis for the role this peptide in pathology Alzheimer's disease. We have introduced sedimentation through ultracentrifugation, either by magic angle spinning (in situ) or preparative ultracentrifuge (ex situ), to immobilize biomolecules and make them amenable solid‐state NMR studies (SedNMR). In situ SedNMR used here address kinetics formation Aβ assemblies monitoring disappearance monomer...
Although the rapid development of sensitivity-enhanced solid-state NMR (ssNMR) spectroscopy based on dynamic nuclear polarization (DNP) has enabled a broad range novel applications in material and life sciences, further methodological improvements are needed to unleash full potential DNP-ssNMR. Here, new methyl-based toolkit for exploring protein structures is presented, which combines signal-enhancement by DNP with heteronuclear Overhauser effect (hetNOE), carbon–carbon-spin diffusion (SD)...
Chromophore perturbations in the sodium transport intermediate states of KR2 are revealed by DNP-enhanced ssNMR.
Dynamic nuclear polarization (DNP) enhances the sensitivity of solid-state NMR (SSNMR) spectroscopy by orders magnitude and, therefore, opens possibilities for novel applications from biology to materials science. This multitude opportunities implicates a need high-performance polarizing agents, which integrate specific physical and chemical features tailored various applications. Here, we demonstrate that biradical bTbK in complex with captisol (CAP), β-cyclodextrin derivative, host-guest...
Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents emerging paradigm infectious disease control. In this scheme, a combination of high efficacy low solubility anti-infection drugs permits the establishment pharmaceutical firewall in HIV-vulnerable groups over long period. Although structure-activity-relationship (SAR) cabotegravir as INSTI known, structural determinants its...
Long-range interactions are crucial in determining the behavior of chemical systems various environments. Accurate predictions physical and phenomena at atomic level hinge on accurate modeling these interactions. Here, we present a framework that substantially enhances predictive power machine learning interatomic potentials by incorporating explicit polarizable long-range with an equivariant graph neural network short-range potential. The pretrained universal model, applicable across entire...
Abstract The RHO gene encodes the G‐protein‐coupled receptor (GPCR) rhodopsin. Numerous mutations associated with impaired visual cycle have been reported; G90D mutation leads to a constitutively active mutant form of rhodopsin that causes CSNB disease. We report on structural investigation retinal configuration and conformation in binding pocket dark light‐activated state by solution MAS‐NMR spectroscopy. found two long‐lived states for 11‐ cis bound as Schiff base both populations. second...
Demetalated superoxide dismutase (SOD1) is a transient species, fibrillogenic in nature and of biomedical interest. It conformationally disordered protein difficult to characterize. We have developed strategy based on the NMR investigation crystalline species characterized by X-ray crystallography comparison solid-state-solution-state chemical shifts. The solid-state assignment has been also helpful assigning solution spectra. spectra presumably detect that are result equilibria among...
Welcome to Annals of Global Health,Annals Health is a peer-reviewed, fully open access, online journal dedicated publishing high quality articles all aspects global health. The journal's mission advance health, promote research, and foster the prevention treatment disease worldwide. Its goals are improve health well-being people, equity, wise stewardship earth's environment. latest impact factor 3.64.Annals supported by Program for Public Common Good at Boston College. It was founded in 1934...