RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2019
·Vol. 34
·期 7
·e8656
·
IF 2.045
Ya-wen Li,Quan Chi,Tao Feng,Huaming Xiao,Linghe Li,Xian Wang
Rationale Interactions of drug molecules and proteins play important roles in physiological and pathological processes in vivo. It is of significance to establish a reliable strategy for studying protein–drug ligand interactions and would be helpful for the design and screening of new drugs in pharmacological research. Methods The interactions between four indole alkaloids (IAs) extracted from Ophiorrhiza japonica ( O. japonica ) and myoglobin (Mb) protein were investigated using a multi-spectrometric and computational method of native electrospray ionization mass spectrometry (native ESI-MS), hydrogen/deuterium exchange mass spectrometry (HDX-MS), circular dichroism (CD) and molecular docking (MD). Results The IA-bound Mb complexes were analyzed using native ESI-MS, with the obtained protein-to-ligand stoichiometry at 1:1, 1:2 and 1:3. Binding constants were measured according to the interpretation of MS spectra. MD complemented MS measurements, probing the binding sites and modes of the four IAs to Mb. Analyses involving CD and HDX-MS demonstrated that exposure to IAs could affect the conformation of Mb by decreasing the α-helix content and made Mb more susceptible to HDX at the backbone. Conclusions A new MS-based integrated analysis method has been developed to successfully study the interactions of Mb and IAs extracted from O. japonica. The experimental and calculation results have good consistency, revealing all of the four IA molecules could bind to Mb to form 1:1, 1:2 and 1:3 Mb–IA complexes. The order of binding ability of these IAs to Mb was ophiorrhine B > compound C > ophiorrhine A > compound D. CD and HDX-MS results indicated that binding with IAs destabilizes Mb. HDX-MS analysis suggests that Mb becomes more susceptible to HDX, indicating that binding with IAs destabilizes the structure of Mb. In addition, the interaction with IAs affected the overall structure of Mb, ascribed to the decrease of α-helix content and less folding of the backbone.
研究领域:
药理学
·
蛋白质组学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FUEL
·
2025
·
IF 7.5
Fange Kong,Ying Zhang,Yilin Liu,Yahe Zhang,Quan Shi,Linzhou Zhang
Different oxygen species exhibit distinct reactivities and properties in fossil fuels such as petroleum and coal liquid products. Elucidating the structural characteristics of these oxygen-containing compounds is essential for effective process design and optimal feedstock selection. The presented study introduces a method combining hydrogen/deuterium exchange (HDX) with high-resolution mass spectrometry to analyze the molecular composition and functional group types of oxygen-containing compounds. Utilizing perdeuterated methanol and toluene as the solvent, we achieved an average HDX depths exceeding 95% across model compounds. The high degree of HDX allows for the inference of oxygen functional groups based on the number of incorporated deuterium atoms. Application to representative fossil fuels (coal tar, coal liquefaction oil, and crude oil) revealed substantial differences oxygen speciation both between different oils and within individual oils. The HDX provided enhanced structural insights into oxygen-containing compounds in coal-derived liquids. Specifically, phenols in coal tar were found to predominantly contain 1–4 hydroxyl groups, with higher-order hydroxylation being negligible. Oxygenated derivatives with dibenzo-α-pyrone core structures were detected as characteristic components in coal-derived products. In contrast, the predominant dioxygenated species in crude oil were carboxylic acids. Furthermore, HDX analysis elucidated the removal selectivity of oxygen functional groups during hydrotreating of coal liquefaction oil.
研究领域:
分析化学
·
能源科学
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2016
·Vol. 8
·期 1
·122-131
·
IF 2.686
Da Ma,Zong-Cai Tu,Hui Wang,Lu Zhang,Na He,David Julian McClements
Tyrosinase is an enzyme that promotes enzymatic browning of fruits and vegetables, thereby reducing product quality. A variety of analytical tools were used to characterize the interactions between tyrosinase and a natural tyrosinase inhibitor (glycolic acid). Hydrogen/deuterium exchange coupling with mass spectrometry (HDX-MS) was used to elucidate the interaction mechanism between glycolic acid and tyrosinase. UV-visible, fluorescence and circular dichroism spectroscopy analysis indicated that glycolic acid inhibited tyrosinase activity in a mixed-type manner with an IC50 of 83 ± 14 μM. The results of these techniques suggested that glycolic acid bound to tyrosinase through hydrophobic attraction, and this interaction led to a pronounced conformational change of the enzyme molecules. HDX-MS analysis showed that the activity of tyrosinase was primarily inhibited by a structural perturbation of its active site (His 263). This study provides a comprehensive understanding of the interaction between glycolic acid and tyrosinase, which could lead to new approaches to control tyrosinase activity in foods and other products.
研究领域:
食品科学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Lewei Zheng,Lingqiao Wang,Dan Li,Chongjun Xie,Zhiyuan Gao,Jinsheng Lin,Jian Ye,Wenbin Chen,Min Li
During the related substances testing of nirmatrelvir , an unknown peak was observed and the level of the peak increased over time during the storage of the sample solution. By using a strategy including LC-PDA/UV-MS n analysis, the degradant was rapidly identified as an epimer of nirmatrelvir, a solution degradation product that is caused by the trace amount of alkaline impurities leaching from the glass HPLC vials. In addition, by using hydrogen/deuterium exchange NMR spectroscopy analysis, the epimerization position was determined to be the carbon α to the adjacent cyano group . Further investigation indicated that the occurrence of the solution degradation can be suppressed when the glass HPLC vials were replaced by plastic HPLC or mass spectrometric grade vials.
研究领域:
药物化学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 145
·期 13
·4442-4451
·
IF 3.978
Ying Zhang,Xiu Chen,Linzhou Zhang,Quan Shi,Suoqi Zhao,Chunming Xu
Hydrotreatment is extensively used for the production of clean fuel. Attaining an understanding of the structural conversion of the nitrogen species during hydrotreatment is very challenging due to the compositional complexity and the absence of a proper characterization method. In the presented work, we coupled hydrogen/deuterium exchange (HDX) with positive-ion electrospray ionization high-resolution mass spectrometry ((+) ESI HR MS) to investigate the difference between the composition of the nitrogen-containing species and the functional groups before and after hydrotreatment. The solvent and additive were optimized for HDX (+) ESI HRMS through systematic evaluations on model nitrogen-containing compounds. We found that adding deuterated water (D2O) and deuterated formic acid (DCOOD) significantly increased the degree of HDX and thus facilitated the identification of nitrogen functional groups. After application to the hydrotreated petroleum samples, the compositional variation of intermediate amine compounds during the heavy petroleum hydrotreatment process was clearly revealed.
研究领域:
化学
·
能源科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry A
·
2020
·Vol. 9
·期 7
·3985-3994
·
IF 11.301
Ruidi Wang,Bei-Bei Xu,Jiachen Wang,Xue Lu Wang,Ye-Feng Yao
The relationship between the structural characteristics and photocatalytic reaction mechanisms of graphitic carbon nitride (g-C3N4) still remains unclarified at the molecular level, which severely hinders the further development of this field. The present study addresses this issue by employing an innovative strategy to investigate the relationship between the H-containing structures of g-C3N4 and its water splitting properties. The exchangeable and unexchangeable protons of the H-containing groups of g-C3N4 were differentiated by selective deuteration, providing a way to distinguish the hydrophilic and relatively non-hydrophilic H-containing groups of g-C3N4. A combination of advanced solid-state NMR approaches reveals that amino group defects (CN2(NHx)) on the C–N skeleton of the photocatalyst likely serve as hydrophilic active sites for facilitating the photocatalytic hydrogen evolution reaction. Accordingly, the newly synthesized g-C3N4 sample having a high concentration of CN2(NHx) by design demonstrates an enhanced H2 yield by a factor of 17 compared to that of pure g-C3N4.
研究领域:
材料化学
·
光催化
·
固体核磁共振
·
表面科学
·
能源材料
✓ 已验证
DOI
高影响因子
NUCLEIC ACIDS RESEARCH
·
2022
·Vol. 50
·期 10
·5850-5863
·
IF 19.16
Lei Yixuan,Fei Panyu,Song Bin,Shi Wenjia,Luo Cheng,Luo Dahai,Li Dan,Chen Wei,Zheng Jie
DDX58 encodes RIG-I, a cytosolic RNA sensor that ensures immune surveillance of nonself RNAs. Individuals with RIG-IE510V and RIG-IQ517H mutations have increased susceptibility to Singleton-Merten syndrome (SMS) defects, resulting in tissue-specific (mild) and classic (severe) phenotypes. The coupling between RNA recognition and conformational changes is central to RIG-I RNA proofreading, but the molecular determinants leading to dissociated disease phenotypes remain unknown. Herein, we employed hydrogen/deuterium exchange mass spectrometry (HDX-MS) and single molecule magnetic tweezers (MT) to precisely examine how subtle conformational changes in the helicase insertion domain (HEL2i) promote impaired ATPase and erroneous RNA proofreading activities. We showed that the mutations cause a loosened latch-gate engagement in apo RIG-I, which in turn gradually dampens its self RNA (Cap2 moiety:m7G cap and N1-2-2′-O-methylation RNA) proofreading ability, leading to increased immunopathy. These results reveal HEL2i as a unique checkpoint directing two specialized functions, i.e. stabilizing the CARD2-HEL2i interface and gating the helicase from incoming self RNAs; thus, these findings add new insights into the role of HEL2i in the control of antiviral innate immunity and autoimmunity diseases.
研究领域:
免疫学
·
分子生物学
·
遗传学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Xin-Yu Xiao,Qian-Wei Luo,Wang-Shu Li,Ze-Kun Chen,Zhuo Yang,Ya-Xuan Zhu,Mu-Rong Lei,Fang-Fang Zhuo,Ming Yu,Tian-Tian Wei,Hong-Wei Jin,Zhong-Yao Li,Zhi-Yuan Lu,Zhu-Qing Zhang,Hua Wang,Yong-Cheng Wang,Qing Xia,Wei Yu,Bo Han,Peng-Fei Tu,Ke-Wu Zeng
Nanoparticles bind to proteins in cells selectively and form a protein corona around them. However, the mechanisms of protein conformational changes underlying the interactions between nanoparticles and protein coronas remain poorly understood. In this study, we prepared small molecule self-assembled nanoparticles (Aloin NPs) as a research tool to investigate the allosteric mechanism of protein coronas. Aloin NPs showed a propensity to capture multiple proteins in cells. In particular, Aloin NPs specifically bound to myotrophin (MPTN) as a major protein corona through a multivalent hydrogen bond-mediated nanoprotein interface. Molecular modeling and hydrogen–deuterium exchange mass spectrometry (MS) demonstrated that Aloin NPs promoted a conformational rearrangement of MPTN via a ‘finger-unclasping’ pattern. We then adapted the APEX2 proximity labeling strategy to investigate the conformation-dependent changes in the MPTN interactome and identified peroxiredoxin 6 (PRDX6) as a key substrate protein of MPTN in microglia. Additionally, we observed that MPTN conformational change-dependent PRDX6 release protected the mitochondrial membrane by reducing reactive oxygen species. Consequently, Aloin NPs effectively inhibited the release of mitochondrial DNA to block the downstream cGAS-STING signaling pathway, thereby reprogramming microglial polarization. In translational medicine, Aloin NPs play a role in protecting neurons from microglia-induced inflammatory injury with no significant adverse effects, ultimately improving Parkinson’s disease-associated symptoms. Taken together, our study provides insights into the molecular mechanisms by which nanoparticles regulate the conformational change of protein coronas for human disease therapy.
研究领域:
纳米技术
·
生物化学
·
细胞生物学
·
神经科学
·
免疫学
·
结构生物学
·
药理学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2023
·
IF 8.8
Yang Yi,Wenzhe Li,Kefang Liu,Heng Xue,Rong Yu,Meng Zhang,Yang-Oujie Bao,Xinyuan Lai,Jingjing Fan,Yuxi Huang,Jing Wang,Xiaomeng Shi,Junhua Li,Hongping Wei,Kuanhui Xiang,Linjie Li,Rong Zhang,Xin Zhao,Xue Qiao,Hang Yang,Min Ye
Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC 50 of 1.016 μM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
研究领域:
病毒学
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
·
2023
·Vol. 26
·期 20
·e202300278
·
IF 2.8
Yonghang Mu,Zi Wang,Linhua Song,Kun Ma,Yao Chen,Peixun Li,Zifeng Yan
Graphical We report a gram-scale synthesis of sphingosines with different deuterated chains. The synthesis of highly stereoselective chain deuterated sphingosine was accomplished in five steps which started from hydrothermal platinum-catalyzed hydrogen/deuterium (H/D) exchange of protiated fatty acids. The subsequent synthesis of the deuterated-chain derivatives are also described. They were all characterized with deuterated content above 94 %. Sphingosine plays crucial roles in various cellular functions. Deuterated molecules are widely used as the important tools to explore the structure, property, and function of biochemical materials. We here report a gram-scale synthesis of sphingosines with different deuterated chains. The synthesis started from different protiated fatty acids, which underwent hydrothermal platinum-catalyzed hydrogen/deuterium (H/D) exchange to produce the deuterated chains with different length. The Horner–Wadsworth–Emmons (HWE) coupling of a chiral amino acid derivative with the deuterated chains generated the unsaturated ketone precursors. The following stereoselective reduction via cyclic Felkin–Anh transition led to the desired anti- amino alcohol geometry. This efficient protocol enabled the gram-scale synthesis of the chain-deuterated sphingosines. The subsequent synthesis of the chain-deuterated derivatives, i. e. ceramide, sphinganine and sphingosine-1-phosphate, is also described. Their deuterium content was simultaneously characterized by 1 H NMR and high-resolution mass spectrum (HRMS).
研究领域:
有机化学
·
生物化学
·
药学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）