INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Caiying Zhang,Yuelong Li,Abdus Samad,Hongliang He,Huan Ma,Yang Chen,Tengchuan Jin
Kyasanur Forest disease virus (KFDV), a tick-borne flavivirus prevalent in India, presents a serious threat to human health. KFDV NS3 helicase (NS3hel) is considered a potential drug target due to its involvement in the viral replication complex. Here, we resolved the crystal structures of KFDV NS3hel apo and its complex with three phosphate molecules, which indicates a conformational switch during ATP hydrolysis . Our data revealed that KFDV NS3hel has a higher binding affinity for dsRNA , and its intrinsic ATPase activity was enhanced by dsRNA while being inhibited by DNA . Through mutagenesis analysis, several residues within motifs I, Ia, III, V, and VI were identified to be crucial for NS3hel ATPase activity. Notably, the M419A mutation drastically reduced NS3hel ATPase activity. We propose that the methionine-aromatic interaction between residues M419 and W294, located on the surface of the RNA-binding channel, could be a target for the design of efficient inhibitor probes. Moreover, epigallocatechin gallate (EGCG), a tea-derived polyphenol, strongly inhibited NS3hel ATPase activity with an IC 50 value of 0.8 μM. Our computational docking data show that EGCG binds at the predicted druggable hotspots of NS3hel. Overall, these findings contribute to the development and design of more effective and specific inhibitors.
研究领域:
病毒学
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结构生物学
·
药物设计
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2022
·Vol. 57
·期 12
·7917-7928
·
IF 3.612
Yu Liu,Zheming Wang,Yizhen Huang,Kunihiko Konno,Tianjian Tong,Chenxu Yu,Beiwei Zhu,Xiuping Dong
Summary The dark muscle of yellowtail kingfish is regularly consumed as fresh sashimi alongside with the ordinary muscle. Thus, in this study, three types of ATPase activities, chymotryptic digestion patterns as well as thermal unfolding of various myosin domains were determined to reveal the denaturation characterisation of myosin in dark muscle and compare it with normal muscle. The thermal inactivation rate of dark muscle myosin Ca 2+ -ATPase at 30°C (7.3 × 10 −4 , sec −1 ) was significantly ( P < 0.05) greater than that of ordinary muscle (5.9 × 10 −4 , sec −1 ), while dark muscle myosin became more stable than ordinary muscle one once bound with F-actin. On the other hand, the rod region especially light meromyosin region of the dark muscle myosin was much more stable than ordinary myosin. These results characterised that myosin in the dark muscle of yellowtail kingfish is constituted with less stable head and more stable rod regions than those in the ordinary muscle.
研究领域:
生物化学
·
肌肉生理学
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DOI
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2018
·Vol. 186
·期 2
·467-473
·
IF 2.361
Cao Changyu,Luo Junchong,Li Xiaowen,Zhang Mengdan,Zhang Haoji,Zhang Jipei,Wang Kai
The aim of this study was to evaluate the protective effects of SeY (selenium-rich yeast) against Al (aluminum)-induced inflammation and ionic imbalances. Male Kunming mice were treated with Al (10 mg/kg) and/or SeY (0.1 mg/kg) by oral gavage for 28 days. The degree of inflammation was assessed by mRNA expression of inflammatory biomarkers. Ionic disorders were assessed by determining the Na + , K + , and Ca 2+ content, as well as the alteration in ATP-modifying enzymes (ATPases), including Na + K + -ATPase, Ca 2+ -ATPase, Mg 2+ -ATPase, Ca 2+ Mg 2+ -ATPase, and the mRNA levels of ATPase’s subunits in kidney. It was observed here that SeY exhibited a significant protective effect on the kidney against the Al-induced upregulation of pro-inflammatory and downregulation of anti-inflammatory cytokines. Furthermore, a significant effect of Al on the Na + , K + , Ca 2+ , and Mg 2+ levels in kidney was observed, and Al was observed to decrease the activities of Na + K + -ATPase, Mg 2+ -ATPase, and Ca 2+ Mg 2+ -ATPase. The mRNA expression of the Na + K + -ATPase subunits and Ca 2+ -ATPase subunits was regulated significantly by Al. Notably, SeY modulated the Al-induced alterations of ion concentrations, ATPase activity, and mRNA expression of their subunits. These results suggest that SeY prevents renal toxicity caused by Al via regulation of inflammatory responses, ATPase activities, and transcription of their subunits.
研究领域:
毒理学
·
营养学
·
分子生物学
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DOI
PubMed
高影响因子
Antibiotics-Basel
·
2024
·Vol. 13
·期 3
·278
·
IF 4.3
Chun Wang,Yun-Yao Ren,Li-Mei Han,Peng-Cheng Yi,Wei-Xiao Wang,Cai-Yun Zhang,Xiu-Zhen Chen,Ming-Zhe Chi,Apeng Wang,Wei Chen,Chun-Mei Hu
Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, includingMycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed byM. smegmatisagainst COG1410 involving ClpC. Upon subjectingM. smegmatisto serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance.
研究领域:
微生物学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
STRUCTURE
·
2025
·
IF 4.3
Shu-Cheng Fang,Liang Wang,Meng-Ting Cheng,Da Xu,Zhi-Peng Chen,Jie Wang,Wenli Liao,Yanyan Li,Cong-Zhao Zhou,Wen-Tao Hou,Yuxing Chen
The human ATP-binding cassette (ABC) transporter ABCA7 participates in the lipidation of apolipoprotein ApoE, a commonly recognized risk factor for Alzheimer’s disease (AD). How ABCA7 is involved in the molecular pathogenesis of AD remains poorly understood. Using cryoelectron microscopy (cryo-EM), we determined ABCA7 structures in the apo and substrate-bound forms, respectively. Combined with activity assays, we assigned the residues that specifically bind two molecules of phosphatidylserine (PS) that are arranged in a “tail-to-tail” manner. Pull-down assays confirmed that ApoE directly interacts with ABCA7; and moreover, both ATPase and lipid transport activities of ABCA7 were significantly enhanced in the presence of ApoE. We also measured the activities of a familial AD variant and a protective clinically reported variant in the ABCA7 gene. Our findings not only give structural insights into ABCA7-mediated PS translocation, but we also provide first biochemical evidence for its link to AD by forwarding lipids to ApoE.
研究领域:
结构生物学
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神经科学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Zhiwen Qi,Xingying Xue,Hao Zhou,Hua Yuan,Wenjun Li,Guliang Yang,Pujun Xie,Chengzhang Wang
To valorise olive mill wastewater phenols (OPs) potentially applied in food preservation, a novel stable and regularly spherical OPs-AgNPs ( D avg = 78 nm) were successfully assembled in aqueous solution under the optimized conditions (pH 8.0, 5 mM AgNO 3 , 35C and 30 min). The results of antimicrobial zone diameters indicated that 50 μg/mL of promising OPs-AgNPs presented excellent antimicrobial effects. Especially, the cell wall damages of E. coli ATCC 23,815 were caused when OPs-AgNPs concentration was exceeded its MIC (8.58 μg/mL). Also, a significant down-regulating of the Ca 2+ -ATPase activity in E. coli was revealed, and the intracellular Ca 2+ concentrations were thus decreased from 12.5 to 1.35 µg/mL after a treatment for 3 h. The apoptosis level of E. coli was significantly increased more than the control (55.13% of OPs-AgNPs vs 9.90% of control). In sum, OPs exerts enhanced antimicrobial function via penetrating cell membrane and targeting Ca 2+ -ATPase after chelated with AgNPs.
研究领域:
环境科学
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材料科学
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微生物学
·
食品科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Lujia Li,Qingxue Fu,Mengxin Xia,Lei Xin,Hongyi Shen,Guowen Li,Guang Ji,Qianchao Meng,Yan Xie
Phytic acid (IP6) is a natural phosphorylated inositol, which is abundantly present in most cereal grains and seeds. This study investigated the effects of IP6 regulation on P-glycoprotein (P-gp) and its potential mechanisms using in situ and in vitro models. The effective permeability of the typical P-gp substrate rhodamine 123 (R123) in colon was significantly increased from (1.69 ± 0.22) × 10–5 cm/s in the control group to (3.39 ± 0.417) × 10–5 cm/s (p < 0.01) in the 3.5 mM IP6 group. Additionally, IP6 can concentration-dependently decrease the R123 efflux ratio in both Caco-2 and MDCK II-MDR1 cell monolayers and increase intracellular R123 accumulation in Caco-2 cells. Furthermore, IP6 noncompetitively inhibited P-gp by impacting R123 efflux kinetics. The noncompetitive inhibition of P-gp by IP6 was likely due to decreases in P-gp ATPase activity and P-gp molecular conformational changes induced by IP6. In summary, IP6 is a promising P-gp inhibitor candidate.
研究领域:
药理学
·
细胞生物学
·
药物递送
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Sihong Li,Ruimeng Liu,Shun Xia,Gaoqiang Wei,Muhammad Ishfaq,Yixin Zhang,Xiuying Zhang
This study set out to assess the mitigative effects of curcumin on AFB1-induced necroptosis and inflammation in chicken liver. Ninety-six one-day-old AA broiler chickens were separated into four groups, including control group, AFB1 (1 mg/kg) group, curcumin (300 mg/kg) + AFB1 (1 mg/kg) group and curcumin (300 mg/kg) group. After 28 days treatment, livers were collected for different experimental analyses. The morphological observation results showed obvious necrotic characteristics, including cell swelling, rupture of cell and mitochondrial membranes and inflammation in chicken livers. AFB1 exposure increased oxidative stress index (ROS and MDA) and decreased the antioxidant activity markers (SOD, CAT and GSH) and ATPase activities in chickens’ liver. ELISA results showed that AFB1 exposure significantly induced the cytokines (TNF-α, iNOS, IL-6 and IL-1β) release from the liver tissues. While, western blot and qRT-PCR results showed that the protein and mRNA expressions of inflammatory (TLR4/myd88/NF-κB) and necroptosis (RIPK1/RIPK3/MLKL) genes were up-regulated by AFB1 exposure. We suspect that signal crosstalk between TLR4 and TNF-α triggers inflammation and RIPK1/RIPK3 mediating necroptosis in AFB1-induced chicken liver injury. Curcumin can regulate the TLR4/RIPK signaling pathway, reduced oxidative stress biomarkers and inflammatory cytokines levels and attenuated the expression of necroptosis and inflammation genes altered by AFB1 to reduce necroptosis of chicken liver tissue. In conclusion, curcumin can protect against AFB1-induced necroptosis and inflammation by TLR4/RIPK pathway in chicken liver.
研究领域:
兽医学
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毒理学
·
分子生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Yajing Fang,Fuqiang Liang,Mengmeng Xia,Weiwei Cao,Siyi Pan,Ting Wu,Xiaoyun Xu
This study was aimed to investigate the inhibitory activity of flavonoids on P-glycoprotein (P-gp). Effects of 39 flavonoids on the cellular uptake (CU) of rhodamine123 (Rho) and daunomycin (DNR) were investigated in both parental KB and P-gp overexpressed KB/MDR cells. The inhibition mechanism of selected flavonoids was further investigated by measuring the ATPase activity and expression level of P-gp. Twelve flavonoids improved the uptake of Rho (↑Rho F ) and nineteen flavonoids increased the uptake of DNR (↑DNR F ) in KB/MDR cells with nine flavonoids overlapped. Structure-activity relationship (SAR) indicated that 8-OCH 3 , and 2′-OH have a negative effect on Rho and DNR transport. Whereas 5-OH, 5-OCH 3 , 6-OH, 7-OCH 3 , 3′-OH, and 4′-OH, are essential for inhibition of flavonoids on P-gp and reversing the resistance of Rho and DNR. Eleven selected flavonoids significantly induced the basal P-gp-ATPase activity but much lower than that induced by verapamil . Tangeretin , galangin , kaempferol , quercetin , and morin significantly reversed the ATPase activity stimulated by verapamil. Six of eleven flavonoids significantly decreased P-gp expression, whereas three flavonoids slightly increased P-gp expression. These results provide valuable information that flavonoids can effectively reverse multidrug resistance of P-gp-mediated transport of nutraceutical and drugs by co-administration.
研究领域:
药理学
·
肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2022
·
IF 6.056
Swati Mahato,Zhiwei Zhu,Da-Wen Sun
Biological interaction with extremely low-frequency electromagnetic fields (ELF-EMF) is complex and the 50 and 60 Hz frequencies are among a few ‘window’ frequency ranges reported with a stimulating effect. In the current study, ELF-EMF at frequencies from 40 to 70 Hz were examined for their possible significance in inducing biological effects during chilled storage of grass carp ( Ctenopharyngodon idellus ) at 4 °C for 4 and 6 h. The myofibrillar protein extracted from the grass carp was analyzed and the results indicate significant (p < 0.05) increases in Ca 2+ ATPase activity and pH, and a reduction in the total sulfhydryl content during the treatment of 50 and 60 Hz frequencies for both storage durations, in particular, the treatment of 50 Hz had pronounced effects with higher correlations. Therefore, the 50 Hz might be associated with the ‘window’ effect, enhancing myofibrillar protein quality during chilled storage.
研究领域:
食品科学
·
生物化学
·
电磁场生物学
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Wenjing Li,Xinru Li,Yajie Gao,Yanxia Zhou,Shujin Ma,Yong Zhao,Jinwen Li,Yan Liu,Xinglin Wang,Dongdong Yin
The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic–lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.
研究领域:
药学
·
药理学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2018
·
IF 2.371
Guan Wang,Manman Liu,Liwei Cao,Jirawat Yongsawatdigul,Shanbai Xiong,Ru Liu
The effect of NaCl (0.1 − 3.0 M) on self-assembly of silver carp myosin at 4 °C was investigated in terms of microstructure, conformation, intermolecular interactions, and particle size distribution. During setting at 4 °C, the self-assembly of myosin showed an obvious concentration dependence. At low concentrations (<0.3 M), myosin assembled into filaments mainly through rod-rod ionic linkages, and showed significantly (P < 0.05) higher turbidity and lower solubility than at ≥0.3 M. The addition of NaCl (0.3 − 0.6 M) led to the extension and dissolution of myosin by interfering with electrostatic interactions. The myosin assemblies gradually became smaller and more uniform. The solubility and Ca 2+ -ATPase activity reached a maximum at 0.6 M NaCl. When the concentrations increased to >1.0 M, myosin further assembled into filaments dominated by hydrophobic interactions. Both rod-rod and head-head interactions contributed to the myosin filaments at high concentrations (1.0 − 3.0 M). The solubility and uniformity of the myosin assemblies decreased as the NaCl concentration increased from 1.0 to 3.0 M.
研究领域:
食品科学
·
蛋白质化学
·
生物物理学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）