Kynurenine aminotransferases (KATs) catalyze the transamination of kynurenine (KYN) pathway and endogenous KYNs have been suggested to highly correlate to abnormal brain diseases. HKAT3 is a key member of KAT family, ...Kynurenine aminotransferases (KATs) catalyze the transamination of kynurenine (KYN) pathway and endogenous KYNs have been suggested to highly correlate to abnormal brain diseases. HKAT3 is a key member of KAT family, while the binding mechanism of KYN and cofactor with HKAT3 has not been determined yet. In this study, we focus on the structure-function relationship among KYN, cofactor and HKAT3. The binding models of KYN complex and KYN&cofactor complex were obtained and were studied by molecular dynamics (MD) simulations. We identified several critical residues and influence of conformational changes in human kynurenine aminotransferase 3 (HKAT3) complexes. The cofactor may contribute largely not only to the catalysis, but also to the binding. In addition, a hypothesis is proposed that a strong hydrophobic interaction between Tyr159 and Lys280 may influence the binding mode and the binding region of the substrate and the cofactor. Our results will be a good starting point for further determination of the biological role.展开更多
Alzheimer's disease(AD) is a progressive neurodegenerative disorder and one of the most common causes of dementia in the elderly.Acetylcholine esterase inhibitors(AChEI) are the main drugs used in the treatment of...Alzheimer's disease(AD) is a progressive neurodegenerative disorder and one of the most common causes of dementia in the elderly.Acetylcholine esterase inhibitors(AChEI) are the main drugs used in the treatment of AD.In this work,docking studies have been performed in order to understand the interaction between a number of inhibitors(tacrine,rivastigmine,huperzine A,TV-3326(ladostigil),donepezil and anseculin) and acetylcholine esterase(AChE).The calculated binding affinities between inhibitors and AChE increase in the order tacrine<rivastigmine<huperzine A<TV-3326<donepezil<anseculin,which reflects the experimental inhibitory activity expressed in terms of the half maximal inhibitory concentration(the IC50 value).Of the above inhibitors,anseculin is the most useful drug for the treatment of dementia.展开更多
t Several molecular simulation methods were integrated to investigate the detailed binding process of allo- phanate to allophanate hydrolase and predict their stable complex structure. The optimal enzyme-substrate com...t Several molecular simulation methods were integrated to investigate the detailed binding process of allo- phanate to allophanate hydrolase and predict their stable complex structure. The optimal enzyme-substrate complex conformation demonstrates that along with Arg307 and Tyr299, Gly124 is also one of the key anchor residues in the stable complex. The energetic calculation suggests the existence of an intermediate state in the enzyme-substrate binding process. The further atomic-level investigation illuminates that Tyr299, Arg307 and Ser172 can stabilize the substrate in the intermediate state. By this token, the residues Arg307 and Tyr299 function in both binding process and getting stable state.展开更多
A novel high selective and sensitive fluorescence probe termed gatifloxacin was discovered based on fluorescence ＂on-off＂ phenomenon in the presence of Se（IV）. In the Tris-HCl/acetonitrile（3：7, volume ratio, Tri...A novel high selective and sensitive fluorescence probe termed gatifloxacin was discovered based on fluorescence ＂on-off＂ phenomenon in the presence of Se（IV）. In the Tris-HCl/acetonitrile（3：7, volume ratio, Tris-HCl 0.05 mol/L, pH=7.3） system, the fluorescence intensity of gatifloxacin was linearly decreased with the concentration increase of Se（IV） in a range of 1.0×10-5--5.0×10-5 mol/L with a correlation coefficient of 0.9979（R2=0.9958） and in a range of 5.0×10-5--1.0 ×10-4 mol/L with a correlation coefficient of 0.9973（R2=0.9946）. The detection limit of Se（IV） was 1.70×10-6mol/L.展开更多
基金supported by the National Natural Science Foundation of ChinaSpecialized Research Fund for the Doctoral Program of Higher EducationSpecialized Fund for the Basic Research of Jilin University (20903045, 20573042, 20070183046,200810018)
文摘Kynurenine aminotransferases (KATs) catalyze the transamination of kynurenine (KYN) pathway and endogenous KYNs have been suggested to highly correlate to abnormal brain diseases. HKAT3 is a key member of KAT family, while the binding mechanism of KYN and cofactor with HKAT3 has not been determined yet. In this study, we focus on the structure-function relationship among KYN, cofactor and HKAT3. The binding models of KYN complex and KYN&cofactor complex were obtained and were studied by molecular dynamics (MD) simulations. We identified several critical residues and influence of conformational changes in human kynurenine aminotransferase 3 (HKAT3) complexes. The cofactor may contribute largely not only to the catalysis, but also to the binding. In addition, a hypothesis is proposed that a strong hydrophobic interaction between Tyr159 and Lys280 may influence the binding mode and the binding region of the substrate and the cofactor. Our results will be a good starting point for further determination of the biological role.
基金Supported by the Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20070183046)the Specialized Fund for the Basic Research of Jilin University (Grant No. 200810018)
文摘Alzheimer's disease(AD) is a progressive neurodegenerative disorder and one of the most common causes of dementia in the elderly.Acetylcholine esterase inhibitors(AChEI) are the main drugs used in the treatment of AD.In this work,docking studies have been performed in order to understand the interaction between a number of inhibitors(tacrine,rivastigmine,huperzine A,TV-3326(ladostigil),donepezil and anseculin) and acetylcholine esterase(AChE).The calculated binding affinities between inhibitors and AChE increase in the order tacrine<rivastigmine<huperzine A<TV-3326<donepezil<anseculin,which reflects the experimental inhibitory activity expressed in terms of the half maximal inhibitory concentration(the IC50 value).Of the above inhibitors,anseculin is the most useful drug for the treatment of dementia.
基金Supported by the International Postdoctoral Exchange Fellowship Program（No.20130037）, the China Postdoctoral Science Foundation（Nos.2013 T60320, 2013M541289）, and the National Natural Science Foundation of China（Nos.21203072, 21303068）.
文摘t Several molecular simulation methods were integrated to investigate the detailed binding process of allo- phanate to allophanate hydrolase and predict their stable complex structure. The optimal enzyme-substrate complex conformation demonstrates that along with Arg307 and Tyr299, Gly124 is also one of the key anchor residues in the stable complex. The energetic calculation suggests the existence of an intermediate state in the enzyme-substrate binding process. The further atomic-level investigation illuminates that Tyr299, Arg307 and Ser172 can stabilize the substrate in the intermediate state. By this token, the residues Arg307 and Tyr299 function in both binding process and getting stable state.
基金Supported by the National Natural Science Foundation of China（No.21207047）, the State Major Project for Science and Technology Development, China（No.2013YQ47078102-3）, the Science-Technology Development Project of Jilin Province of China（Nos.20130206014GX, 20140623007TC, 20150204017YY）, the Open Project of the State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, China（No.2014-07） and the Natural Science Foundation of Jilin Province, China（No.20160101314JC）.
文摘A novel high selective and sensitive fluorescence probe termed gatifloxacin was discovered based on fluorescence ＂on-off＂ phenomenon in the presence of Se（IV）. In the Tris-HCl/acetonitrile（3：7, volume ratio, Tris-HCl 0.05 mol/L, pH=7.3） system, the fluorescence intensity of gatifloxacin was linearly decreased with the concentration increase of Se（IV） in a range of 1.0×10-5--5.0×10-5 mol/L with a correlation coefficient of 0.9979（R2=0.9958） and in a range of 5.0×10-5--1.0 ×10-4 mol/L with a correlation coefficient of 0.9973（R2=0.9946）. The detection limit of Se（IV） was 1.70×10-6mol/L.
