Scientific Reports
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2018
·Vol. 8
·期 1
·1-11
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IF 4.122
Xiao Qiling,Zhou Qiongqiong,Yang Lu,Tian Zhongyuan,Wang Xiliang,Xiao Yuncai,Shi Deshi
Human carboxylesterases has been proven to be age and race-related and a sound basis of clinical medication. PLE involve in signal transduction and highly catalyze hydrolysis. Therefore, the expression level of PLE most probably exist age and breed difference and lead to significant differences of pharmacology and physiology. Four age groups of Tongcheng (TC) and Large White (LW) pigs were selected to explore PLE breed and age differences, and it was found that PLE mRNA was most abundant in liver in both breeds. In liver, PLE levels and hydrolytic activities increased with age, and PLE levels (except for 3 month) and the hydrolytic activities were higher in LW than in TC across all age groups. Abundance of PLE isoenzymes was obvious different between breeds and among age groups. The most abundant PLE isoenzyme in LW and TC pigs was PLE-A1 (all age groups) and PLE-B9 (three early age groups) or PLE-G3 (adult groups), respectively. 103 new PLE isoenzymes were found, and 55 high-frequency PLE isoenzymes were accordingly classified into seven categories (A-G). The results of this research provide a necessary basis not only for clinical medication of pigs but also for pig breeding purposes.
研究领域:
兽医学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
CATALYSIS LETTERS
·
2021
·Vol. 152
·期 9
·2625-2636
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IF 3.186
Li Qi,Chai Changsheng,Zhao Linguo
In this paper, five recombinant strains: GS115-LacA, GS115-LacB, GS115-LacC, KM71H-Lcc1 and GS115-Lcc2 were selected to produce laccase isozymes with high activities, which reached 13,001 U/L, 10,254 U/L, 11,495 U/L, 9924 U/L and 10,031 U/L on 15th, respectively. Then, we investigated the specificity of several recombinant laccase isozymes for the degradation of endocrine disrupting chemicals (phenolic compounds). The results showed that LacB had the most efficient in degradation of bisphenol A and octyl phenol, while Lcc1 degraded 4- n -octylphenol, gossypol and hydroquinone better. Finally, the effects of degradation conditions were optimized, which shown that the degradation rates of phenolic compounds increased with the optimum temperature and pH by different laccases were different, which were closely related to their enzymatic properties. Under the optimum reaction conditions, the degradation rate of bisphenol A, gossypol, 4- n -octylphenol, octyl phenol and hydroquinone were 95.4%, 93.2%, 89.6%, 71.0% and 91.9% at 8 h, 8 h, 12 h, 24 h and 1 h, respectively. Furthermore, the recombinant laccases were used to degrade phenolic compounds in several laccase/mediator systems, which ABTS and vanillin showed most enhancement on degradation rates and reduction of degradation times. In LacB-ABTS and Lcc1-guaiacol/vanillin systems, the degradation rates of five phenolic compounds reached the maximum with totally 100% within 4 h. All of the results open up promising perspectives for the degradation and oxidative biotransformation of typical phenolic pollutants in the environment. Graphical Abstract
研究领域:
环境科学
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生物技术
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酶学
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DOI
高影响因子
Food & Function
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2018
·Vol. 9
·期 11
·5547-5559
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IF 3.289
Peng Yang,Guo-Bin Ding,Wen Liu,Rong Fu,Amin Sajid,Zhuoyu Li
Tannic acid (TA), a naturally occurring polyphenolic acid that is primarily found in grapes and green tea, exhibits potent antioxidant and anticarcinogenic characteristics. However, the underlying molecular mechanisms and targets of TA, which are responsible for cancer prevention, remain elusive. In the present study, we used TA-functionalized magnetite nanoparticles to identify pyruvate kinase isoenzyme M2 (PKM2) as the direct target of TA. We report that TA selectively inhibits the pyruvate kinase activity of PKM2, rather than protein kinase activity and PKM2 expression, to suppress colorectal cancer (CRC) cell proliferation. Furthermore, we had discovered that lysine residue 433 (K433) is a selective druggable site. Through direct binding to lysine residue 433, TA triggers the dissociation of PKM2 tetramers and further blocks the metabolic activity of PKM2. Notably, TA has no effect on PKM1 activity as TA does not bind to it. Taken together, these findings show that TA is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Dan Ma,Yang Lyu,Yujia Wang,Xiaochen Li,Junheng Wang,Yingying Wang,Sijun Dong
Phthalates (PAEs), such as dibutyl phthalate (DBP), are emerging contaminants in agriculture that are commonly used in plastic films, pesticides, and soil amendments. Their accumulation in water threatens ecosystems and human health. Biodegradation offers a promising solution, but the DBP degradation mechanisms remain unclear. This study identified two 4,5-PCD isoenzymes (PCD34 and PCD67) in Curvibacter sp. PAE-UM. PCD34 showed higher affinity and broader substrate specificity, while PCD67 had better thermal stability and metal ion sensitivity. Both enzymes converted protocatechuate (PCA) to 4CHMS at 45% efficiency in 5 min. Molecular dynamics revealed the stable binding of PCD67, while mutagenesis enhanced PCD34 activity (124.4%) by reducing steric hindrance. These findings may aid in the engineering of strains for PAE bioremediation in agricultural wastewater.
研究领域:
环境微生物学
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生物技术
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酶学
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分子生物学
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生态毒理学
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DOI
PubMed
高影响因子
ADVANCED SYNTHESIS & CATALYSIS
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2017
·Vol. 359
·期 7
·1185-1193
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IF 5.646
Yu-Cong Zheng,Jian-He Xu,Hui Wang,Guo-Qiang Lin,Ran Hong,Hui-Lei Yu
Biocatalysts originating from Badamu ( Prunus communis ) have been applied to catalyze the asymmetric synthesis of ( R )-4-methylsulfanylmandelonitrile, a key building block of thiamphenicol and florfenicol. Here, four hydroxynitrile lyase (HNL) isozymes from Badamu were cloned and heterologously expressed in Pichia pastoris . The biochemical properties and catalytic performances of these isozymes were comprehensively explored to evaluate their efficiency and selectivity in asymmetric synthesis. Among then, Pc HNL5 was identified with outstanding activity and enantioselectivity in asymmetric hydrocyanation. Under the optimized mild biphasic reaction conditions, seventeen prochiral aromatic aldehydes were converted to valuable chiral cyanohydrins with good yields (up to 94%) and excellent optical purities (up to >99.9% ee ), which provide a facile access to numerous chiral amino alcohols, hypoglycemic agents, angiotension converting enzyme (ACE) inhibitors and β-blockers. This work therefore underlines the importance of discovering the most potent biocatalyst among a group of isozymes for converting unnatural substrates into value-added products.
研究领域:
生物化学
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生物技术
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酶学
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有机化学
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药物化学
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产品关联
DOI
高影响因子
AAPS Journal
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2013
·Vol. 16
·期 1
·101-113
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IF 4.386
Qiao Xue,Ji Shuai,Yu Si-wang,Lin Xiong-hao,Jin Hong-wei,Duan Yao-kai,Zhang Liang-ren,Guo De-an,Ye Min
Licorice has been shown to affect the activities of several cytochrome P450 enzymes. This study aims to identify the key constituents in licorice which may affect these activities. Bioactivity assay was combined with metabolic profiling to identify these compounds in several complex licorice extracts. Firstly, the inhibition potencies of 40 pure licorice compounds were tested using an liquid chromatography/tandem mass spectrometry cocktail method. Significant inhibitors of human P450 isozymes 1A2, 2C9, 2C19, 2D6, and 3A4 were then selected for examination of their structural features by molecular docking to determine their molecular interaction with several P450 isozymes. Based on the present in vitro inhibition findings, along with our previous in vivo metabolic studies and the prevalence of individual compounds in licorice extract, we identified several licorice constituents, viz ., liquiritigenin, isoliquiritigenin, together with seven isoprenylated flavonoids and arylcoumarins, which could be key components responsible for the herb–drug interaction between cytochrome P450 and licorice. In addition, hydrophilic flavonoid glycosides and saponins may be converted into these P450 inhibitors in vivo . These studies represent a comprehensive examination of the potential effects of licorice components on the metabolic activities of P450 enzymes.
研究领域:
药理学
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分析化学
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生物化学
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药学
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DOI
PubMed
高影响因子
Cell Host & Microbe
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2025
·
IF 18.7
Hongbin Liu,Juntao Shen,Zhiwei Zhang,Jiuming Wang,Chengxin Zhang,Linggang Zheng,Haoran Ni,Liang Hong,Jieqiong Zhang,Dongfang Xue,Jiayang Chen,Qinze Yu,Zepeng Qu,Yingfei Ma,Tong Si,Liangzhen Zheng,Sheng Wang,Changtao Jiang,Yu Li,Kai Wang,Lei Dai
The human gut microbiome contains numerous proteins whose functions remain elusive yet are pivotal to host health. Sequence-based methods often falter when attempting to infer functions within this microbial proteome due to evolutionary divergence. To address this challenge, we develop the Human Gut Microbial Protein Structure Database, which incorporates ∼2.7 million predicted protein structures. Our findings reveal that structural analogy enhances the annotation of phage proteins. We detail the structural diversification of phage endolysins and confirm their potential in eliminating gut pathobionts. Furthermore, our structure-guided approach is effective in the identification of microbial-host isozymes. By employing structural alignments, we identify previously unrecognized bacterial enzymes involved in melatonin biosynthesis. Finally, we present an alignment-free method, dense enzyme retrieval, based on structure-encoded protein language models for ultrafast and sensitive detection of remote homologs. Our research underscores the value of computational structural genomics in elucidating the functional landscape of the human gut microbiome.
研究领域:
微生物组研究
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结构生物信息学
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计算生物学
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宏基因组学
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酶发现
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Xiu Huang,Yong Li,Zhao Shu,Li Huang,Qian Liu,Guibin Jiang
Plastic pollution is a significant environmental concern globally. Plastics are normally considered chemically inert and resistant to biodegradation. Although many papers have reported enzyme-induced biodegradation of plastics, these studies are primarily limited to enzymes of microbial origin or engineered enzymes. This study reveals that poly(ethylene terephthalate) (PET, ∼6000 Da and 100 kDa) particles and plastic bottle debris (PBD, 24.9 kDa) can be efficiently degraded by a mammal-origin natural phase II metabolic isozyme, glutathione S-transferase (GST), under mild conditions. The degradation efficiency of PET plastics reached 98.9%, with a degradation rate of 2.6 g·L–1·h–1 under ambient or physiological conditions at 1 atm. PET plastics can be degraded by GST with varying environmental or biological factors (i.e., temperature, light irradiation, pH, and presence of humic acid or protein). We suggest a novel mechanism for PET degradation other than hydrolysis, i.e., the mechanism of cleavage and release of PET plastic monomers via nitridation and oxidation. This finding also reveals a novel function of GST, previously thought to only degrade small molecules (<1000 Da). This method has been successfully applied in real human serum samples. Additionally, we have tested and confirmed the ability to degrade PET of a mammal-origin natural digestive enzyme (trypsin) and a human-derived natural metabolic enzyme (CYP450). Overall, our findings provide a potential new route to plastic pollution control and contribute to our understanding of the metabolism and fate of plastics in organisms.
研究领域:
环境科学
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生物化学
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生物技术
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酶学
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产品关联
DOI
PubMed
高影响因子
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