RSC Advances
·
2017
·Vol. 7
·期 60
·37636-37642
·
IF 3.108
Qiao-Feng Zheng,Mo Yu,Shu-Shen Liu,Fu Chen
Hormesis is a biphasic concentration–response relationship. During the luminescence inhibition test of Vibrio qinghaiensis sp.-Q67 (Q67), some organic solvents display the hormesis phenomenon. However, the mechanism of hormesis with respect to organic solvents remains unclear. This study focuses on luciferase, which is the key factor in luminescent reactions, and explores its role in the mechanism of hormesis. Q67 luciferase has two subunits, α and β. Molecular docking and molecular dynamics simulations were carried out by taking organic solvents as ligand and the two subunits as receptor. In addition, the binding free energies of the complexes formed by the ligand and Q67 luciferase were calculated. The results showed that the organic solvent ligands exhibiting hormesis bind to the β subunit first, while those that do not exhibit hormesis bind more easily to the α subunit. The hormetic organic solvents bind to β subunit first at low concentration, and change the flexibility of residues Ser145–Arg165 located on the α subunit; this enables flavin mononucleotide (FMN) to bind to the α subunit, exhibiting the hormesis phenomenon. With the increasing concentration, redundant molecules start to bind to the α subunit and compete with/block FMN binding to the α subunit, resulting in inhibition.
研究领域:
生物化学
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分子生物学
·
环境毒理学
✓ 已验证
DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2018
·Vol. 102
·期 18
·7891-7900
·
IF 3.34
Pei Xiaolin,Wang Jiapao,Wu Yifeng,Zhen Xiaoting,Tang Manman,Wang Qiuyan,Wang Anming
Nitrile hydratase (NHase) has attracted considerable attention since it can efficiently catalyze the hydration of nitriles to valuable amides. However, the poor stability of NHase is one of the main drawbacks in the industrial application. In this study, we compared the structural difference between Fe-type and Co-type NHase and found that an extra α helix existed at the β-subunit surface of Co-type NHase (defined as the β-6th helix). Then, the effects of the β-6th helix were investigated on the thermal stability and the catalytic kinetics of a Co-type NHase from Aurantimonas manganoxydans ATCC BAA-1229 (NHase1229). When the β-6th helix was deleted or disrupted, the thermal stability of NHase1229 was reduced to 17.6 and 12.9% of that of wild NHase1229, respectively. Thus, the β-6th helix is important for the thermal stability of Co-type NHase. Based on the structural characteristics of Co-type NHase, the β-6th helix may be interacted with another helix at the α-subunit (defined as the α-2nd helix) by hydrophobic network just as a “magnetic suction buckle” on the enzyme surface to stabilize the binding of α- and β-subunits. The β-6th helix is located at the mouth of the substrate and product tunnel, so it plays crucial roles in catalytic process. Furthermore, the β-6th helix in NHase1229 was swapped with a thermophilic NHase fragment from Pseudonocardia thermophila JCM3095 (NHase1229-Swap). The thermal stability of NHase1229-Swap was significantly improved, and the half-life was approximately 2.4-fold at 40 °C than that of the wild NHase1229. The knowledge is useful for improving the stability of NHases by restriction fragment swapping.
研究领域:
生物化学
·
酶工程
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Yu Ma,Wei Yang,Peiyao Liang,Ruzhen Feng,Tianming Qiu,Jingyuan Zhang,Xiance Sun,Qiujuan Li,Guang Yang,Xiaofeng Yao
As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity.
研究领域:
毒理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Integrative Neuroscience
·
2024
·Vol. 23
·期 8
·145
·
IF 2.5
Yuan Xu,Yushi Yang,Jie Yang,Junshuan Cui,Jian Yan,Jiannan Jiang,Zhangwei Yan,Hua Yang
Background: Ischemic stroke is mainly caused by cerebral artery thrombosis. This study investigated the role of glycine receptor beta subunit (GlyR-β) in the recovery from cerebral ischemia stroke/reperfusion. Methods: The oxygen glucose deprivation and recovery (OGD/R) bEnd3 cell model and the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model were used in this study. Results: Expression of both the GlyR-β gene and vascular endothelial growth factor (Vegf), cell proliferation, and tube formation ability was decreased in bEnd3 cells after OGD/R, and was reversed by overexpression of GlyR-β. Neurological function, asindicated by Zea Longa scores, area of cerebral ischemia, and pathological changes were increased in mice after MCAO/R, and were ameliorated by overexpression of the glycine receptor beta (Glrb) gene at 24 h and 7 d after MCAO/R. Expression of GlyR-β and Gap-43 was decreased, and the expression of CD34, Vegf, and Bdnf, and cell growth as determined by a bromodeoxyuridine (BrdU) assay, increased in the affected brain tissue of MCAO/R mice in a time-dependent manner. GlyR-β overexpression resulted in enhanced expression of CD34, Vegf, Growth association protein 43 (Gap-43), and brain-derived neurotrophic factor (Bdnf) and cell growth in affected brain tissue of MCAO/R mice in a time-dependent manner. Conclusions: GlyR-β promoted potential angiogenesis and neurological regeneration in affected brain tissue, thus promoting recovery from cerebral ischemia stroke/reperfusion.
研究领域:
神经科学
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分子生物学
·
药理学
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病理生理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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