Publications by authors named "Xuncheng Su"

Due to their exceptional anisotropic magnetic properties, lanthanide ion (Ln) complexes are of great utility in many fields of chemistry, including magnetic materials, biomedical imaging, and nuclear magnetic resonance (NMR) spectroscopy. How to achieve large magnetic anisotropies in the Ln complexes coordinated with open-chain ligands is still a challenge. In this study, we started from the open-chain 4PS-PyMTA ligand and assessed the magnetic anisotropy using installed Ln coordinating pendants by increasing size and rigidity.

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Isoaspartate (isoAsp) is a β-linked residue in proteins spontaneously generated through Asn deamidation or Asp dehydration and significantly affects protein properties. However, the sluggish and site-nonselective generation of isoAsp residues in proteins severely impedes in-depth biological investigations as well as the exploitation of its unique β-linkage features. Herein, we introduce a method that allows site-selective and rapid generation of isoAsp residues in proteins.

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Aldehyde represents an extremely useful bio-orthogonal group in chemical biology and has promoted the generation of high-quality bioconjugates in therapeutics development. However, the installation of an aldehyde group on a protein and subsequent conjugation remains technically inadequate in the aspect of site choice, substrate availability, and linkage stability. Herein, we take efforts to advance the genetic incorporation of an aldehyde-containing noncanonical amino acid in and then show that reductive amination could be a useful reaction in introducing various amine-containing molecules, including peptides, into a specific site of proteins.

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The death domain (DD) superfamily, a group of protein interaction modules, plays a crucial role in regulating downstream signaling pathways through the formation of specific complexes. However, the aggregation-prone behavior of many DD superfamily members in solution limits their interaction studies, and the structural mechanisms underlying oligomeric assembly involving different DD subfamilies are not fully understood. Here, we demonstrate that RIP2-CARD retains its native folding and protein function for interacting with the DD of p75 neurotrophin receptor (p75) in pure water rather than under acidic conditions of pH 5.

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Background: Human papillomavirus (HPV) is a prevalent infection affecting both men and women, leading to various cytological lesions. Therapeutic vaccines mount a HPV-specific CD8+ cytotoxic T lymphocyte response, thus clearing HPV-infected cells. However, no therapeutic vaccines targeting HPV are currently approved for clinical treatment due to limited efficacy.

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Pulsed dipolar electron paramagnetic resonance (PD-EPR) measurement is a powerful technique for characterizing the interactions and conformational changes of biomolecules. The extraction of these distance restraints from PD-EPR experiments relies on manipulation of spin-spin pairs. The orthogonal spin labeling approach offers unique advantages by providing multiple distances between different spin-spin pairs.

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Pseudocontact shift (PCS) contains rich structural information of proteins in structural and chemical biology. F-PCS is determined in live mammalian cells dual labelling of the target protein with a paramagnetic tag and a F-tag, which is achieved by varied reactivity of solvent exposed cysteines in selection of different types of tags. About 0.

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Article Synopsis
  • - F electron-nuclear double resonance (ENDOR) is shown to be effective for measuring distances in biomolecules (0.7-2 nm) that traditional methods struggle with, using various spin labels.
  • - The study compares different spin labels, such as nitroxide, trityl radicals, Gd(III) chelates, and Cu(II) nitrilotriacetic acid chelates, using GB1 and ubiquitin proteins, revealing Gd(III) chelates yield the best signal-to-noise ratio.
  • - Findings indicate that the new trityl label, OXMA, has a long phase memory time but a longer tether limits its distance measurement capabilities; Gd(III) labels provide the most
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Photocaged amino acids could be genetically encoded into proteins via genetic code expansion (GCE) and constitute unique tools for innovative protein engineering. There are a number of photocaged proteinogenic amino acids that allow strategic conversion of proteins into their photocaged variants, thus enabling spatiotemporal and non-invasive regulation of protein functions using light. Meanwhile, there are a hand of photocaged non-proteinogenic amino acids that address the challenges in directly encoding certain non-canonical amino acids (ncAAs) that structurally resemble proteinogenic ones or possess highly reactive functional groups.

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The combined effects of the cellular environment on proteins led to the definition of a fifth level of protein structural organization termed quinary structure. To explore the implication of potential quinary structure for globular proteins, we studied the dynamics and conformations of Escherichia coli (E. coli) peptidyl-prolyl cis/trans isomerase B (PpiB) in E.

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Site-specific modification of proteins with synthetic fluorescent tag effectively improves the resolution of imaging, and such a labeling method with negligible three-dimensional structural perturbations and minimal impact on the biological functions of proteins is of high interest to dissect the high-resolution activities of biomolecules in complex systems. To this end, several non-emissive iridium(III) complexes [Ir(C-N) (H O) ] OTF (C-N denotes various cyclometalated ligands) were designed and synthesized. These complexes were tested for attaching a protein by coordinating to H/X (HisMet, HisHis, and HisCys) that are separated by i and i+4 in α-helix.

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Heat shock protein 90 (Hsp90) serves as a crucial regulator of cellular proteostasis by stabilizing and regulating the activity of numerous substrates, many of which are oncogenic proteins. Therefore, Hsp90 is a drug target for cancer therapy. Hsp90 comprises three structural domains, a highly conserved amino-terminal domain (NTD), a middle domain (MD), and a carboxyl-terminal domain (CTD).

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2D NOESY and TOCSY play central roles in contemporary NMR. We have recently discussed how solvent-driven exchanges can significantly enhance the sensitivity of such methods when attempting correlations between labile and nonlabile protons. This study explores two scenarios where similar sensitivity enhancements can be achieved in the absence of solvent exchange: the first one involves biomolecular paramagnetic systems, while the other involves small organic molecules in natural abundance.

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Visualization and quantification of important biomolecules like glutathione (GSH) in live cells are highly important. The existing methods are mostly from optical detection and lack of atomic resolution on the activity of GSH. Here, we present a sensitive F-NMR method to quantify real-time variations of GSH in live cells in a reversible manner.

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Genetically replacing an essential residue with the corresponding photocaged analogues via genetic code expansion (GCE) constitutes a useful and unique strategy to directly and effectively generate photoactivatable proteins. However, the application of this strategy is severely hampered by the limited number of encoded photocaged proteinogenic amino acids. Herein, we report the genetic incorporation of photocaged glutamic acid analogues in E.

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We report an effective assessment of lanthanide ion (Ln) delivery into live cells by paramagnetic NMR spectroscopy. Free Ln ions are toxic to live cells resulting in a gradual leakage of target proteins to the extracellular media. The citrate-Ln complex is an efficient and mild reagent over the free Ln form for live cell delivery.

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p75 neurotrophin receptor (p75) contains a C-terminal globular protein module known as the death domain (DD), which plays a central role in apoptotic and inflammatory signaling through the formation of oligomeric protein complexes. A monomeric state of the p75-DD also exists depending on its chemical environment in vitro. However, studies on the oligomeric states of the p75-DD have produced conflicting findings and sparked great controversy.

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Nitroxide (NO) spin radicals are effective in characterizing structures, interactions and dynamics of biomolecules. The EPR applications in cell lysates or intracellular milieu require stable spin labels, but NO radicals are unstable in such conditions. We showed that the destabilization of NO radicals in cell lysates or even in cells is caused by NADPH/NADH related enzymes, but not by the commonly believed reducing reagents such as GSH.

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Article Synopsis
  • Half-Integer High Spin (HIHS) systems with low Zero-Field Splitting (ZFS) are typically studied at the central transition (CT) for optimal sensitivity in EPR experiments.
  • This research details a method using WURST pulses to shift spin populations from the CT to higher spin transitions, specifically to Gd(III) complexes.
  • The results show over a two-fold increase in sensitivity for H Mims ENDOR measurements at Q- and W-band frequencies, allowing for improved experiments at elevated temperatures and with various pulse sequences.
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Studies of protein structure and dynamics are usually carried out in dilute buffer solutions, conditions that differ significantly from the crowded environment in the cell. The double electron-electron resonance (DEER) technique can track proteins' conformations in the cell by providing distance distributions between two attached spin labels. This technique, however, cannot access distances below 1.

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High performance in chiral recognition by a reactive F-tag was demonstrated for a variety of enantiomers. The analytes with up to five flexible covalent bonds from the chiral center can be discriminated by a sensitive chiral reporter manifested in the F-NMR spectrum. Simultaneous identification of chiral amines in a mixture and high accuracy ee determination were achieved.

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Fluorinated nucleotides are invaluable for F NMR studies of nucleic acid structure and function. Here, we synthesized 4'-SCF -thymidine (T ) and incorporated it into DNA by means of solid-phase DNA synthesis. NMR studies showed that the 4'-SCF group exhibited a flexible orientation in the minor groove of DNA duplexes and was well accommodated by various higher order DNA structures.

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The application of umbilical cord blood (UCB) as an important source of hematopoietic stem and progenitor cells (HSPCs) for hematopoietic reconstitution in the clinical context has steadily grown worldwide in the past 30 years. UCB has advantages that include rapid availability of donors, less strict HLA-matching demands, and low rates of graft-versus-host disease (GVHD) versus bone marrow (BM) and mobilized peripheral blood (PB). However, the limited number of HSPCs within a single UCB unit often leads to delayed hematopoietic engraftment, increased risk of transplant-related infection and mortality, and proneness to graft failure, thus hindering wide clinical application.

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Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been approved for clinical use. SARS-CoV-2 neutralizing antibody titers after immunization are widely used as an evaluation indicator, and the roles of cellular immune responses in the protective efficacy of vaccines are rarely mentioned. However, therapeutic monoclonal neutralizing antibodies have shown limited efficacy in improving the outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19), suggesting a passive role of cellular immunity in SARS-CoV-2 vaccines.

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Flexibility between the paramagnetic tag and its protein conjugates is a common yet unresolved issue in the applications of paramagnetic NMR spectroscopy in biological systems. The flexibility greatly attenuates the magnetic anisotropy and compromises paramagnetic effects especially for pseudocontact shift and residual dipolar couplings. Great efforts have been made to improve the rigidity of paramagnetic tag in the protein conjugates, however, the effect of local environment vicinal to the protein ligation site on the paramagnetic effects remains poorly understood.

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