Calmodulin(CaM) is involved in the regulation of a variety of cellular signaling pathways. To accomplish its physiological functions, CaM binds with Ca^(2+) at its EF-hand Ca^(2+) binding sites which induce the confor...Calmodulin(CaM) is involved in the regulation of a variety of cellular signaling pathways. To accomplish its physiological functions, CaM binds with Ca^(2+) at its EF-hand Ca^(2+) binding sites which induce the conformational switching of CaM. However, the molecular mechanism by which Ca^(2+) binds with CaM and induces conformational switching is still obscure. Here we combine molecular dynamics with targeted molecular dynamics simulation and achieve the state-transition pathway of CaM. Our data show that Ca^(2+) binding speeds up the conformational transition of CaM by weakening the interactions which stabilize the closed state. It spends about 6.5 ns and 5.25 ns for transition from closed state to open state for apo and holo CaM, respectively. Regarding the contribution of two EF-hands, our data indicate that the first EF-hand triggers the conformational transition and is followed by the second one. We determine that there are two interaction networks which contribute to stabilize the closed and open states, respectively.展开更多
Phospholipid hydroperoxide glutathione peroxidase is an antioxidant enzyme that has the highest capability of reducing membrane-bound hydroperoxy lipids as compared to free organic and inorganic hydroperoxides amongst...Phospholipid hydroperoxide glutathione peroxidase is an antioxidant enzyme that has the highest capability of reducing membrane-bound hydroperoxy lipids as compared to free organic and inorganic hydroperoxides amongst the glutathione peroxidases.In this study,urea-induced effects on the inactivation and unfolding of a recombinant phospholipid hydroperoxide glutathione peroxidase(PHGPx)from Oryza sativa were investigated by means of circular dichroism and fluorescence spectroscopy.With the increase of urea concentration,the residual activity of OsPHGPx decreases correspondingly.When the urea concentration is above 5.0 mol/L,there was no residual activity.In addition,the observed changes in intrinsic tryptophan fluorescence,the binding of the hydrophobic fluorescence probe ANS,and the far UV CD describe a common dependence on the concentration of urea suggesting that the conformational features of the native OsPHGPx are lost in a highly cooperative single transition.The unfolding process comprises of three zones:the native base-line zone between 0 and 2.5 mol/L urea,the transition zone between 2.5 and 5.5 mol/L urea,and the denatured base-line zone above 5.5 mol/L urea.The transition zone has a midpoint at about 4.0 mol/L urea.展开更多
Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin hav...Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin have already been investigated.However,the conformation transitions induced by cisplatin are not clear.In the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM imaging.We observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod structures.We found that the formation of micro-rod structures depends on the DNA sequence.Based on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.展开更多
Much attention has been paid to the natural mechanism of silkworm spinning due to the impressive me-chanical properties of the natural fibers. In this work, we studied the effect of Cu(II) ions on the secondary struct...Much attention has been paid to the natural mechanism of silkworm spinning due to the impressive me-chanical properties of the natural fibers. In this work, we studied the effect of Cu(II) ions on the secondary structure of Bombyx mori regenerated silk fibroin (SF) in dilute solution by circular dichroism (CD). The results indicate that a given amount of Cu(II) induces the SF conformational transition from random coil to β-sheet, however, further addition of Cu(II) is unfavorable for this conversion. Meanwhile, the conformational changes induced by Cu(II) follow a nuclea-tion-dependent aggregation mechanism, which is similar to that found in Prion protein (PrP) denaturation and Aβ-pep- tide aggregations, leading to the neurodegenerative disease. This work would help one understand further the natural spinning process of silkworm. Additionally, it would be sig-nificant for the study of the nervous system diseases, because silk fibroin, extracted in large amounts from Bombyx mori silkworm gland, could be a proper model to study PrP dena-turation and Aβ-peptide aggregations.展开更多
基金Supported by the Natural Science Fund for Distinguished Young Scholars of Hebei Province under Grant Nos C2015202340 and C2013202244the Fund for Outstanding Talents of Hebei Province under Grant No C201400305+3 种基金the National Natural Science Fund of China under Grant Nos 11247010,11175055,11475053,11347017,31600594,31400711 and 11647121the Fund for the Science and Technology Program of Higher Education Institutions of Hebei Province under Grant No QN2016113the Scientific Innovation Grant for Excellent Young Scientists of Hebei University of Technology under Grant No 2015010the Natural Science Foundation of Hebei Province under Grant No C2017202208
文摘Calmodulin(CaM) is involved in the regulation of a variety of cellular signaling pathways. To accomplish its physiological functions, CaM binds with Ca^(2+) at its EF-hand Ca^(2+) binding sites which induce the conformational switching of CaM. However, the molecular mechanism by which Ca^(2+) binds with CaM and induces conformational switching is still obscure. Here we combine molecular dynamics with targeted molecular dynamics simulation and achieve the state-transition pathway of CaM. Our data show that Ca^(2+) binding speeds up the conformational transition of CaM by weakening the interactions which stabilize the closed state. It spends about 6.5 ns and 5.25 ns for transition from closed state to open state for apo and holo CaM, respectively. Regarding the contribution of two EF-hands, our data indicate that the first EF-hand triggers the conformational transition and is followed by the second one. We determine that there are two interaction networks which contribute to stabilize the closed and open states, respectively.
基金Supported by the National Basic Research Program of China(No.2006CB101706)the Hi-tech Research and DevelopmentProgram of China(No.2007AA100604)the National Natural Science Foundation of China(Nos.30170080and39770078).
文摘Phospholipid hydroperoxide glutathione peroxidase is an antioxidant enzyme that has the highest capability of reducing membrane-bound hydroperoxy lipids as compared to free organic and inorganic hydroperoxides amongst the glutathione peroxidases.In this study,urea-induced effects on the inactivation and unfolding of a recombinant phospholipid hydroperoxide glutathione peroxidase(PHGPx)from Oryza sativa were investigated by means of circular dichroism and fluorescence spectroscopy.With the increase of urea concentration,the residual activity of OsPHGPx decreases correspondingly.When the urea concentration is above 5.0 mol/L,there was no residual activity.In addition,the observed changes in intrinsic tryptophan fluorescence,the binding of the hydrophobic fluorescence probe ANS,and the far UV CD describe a common dependence on the concentration of urea suggesting that the conformational features of the native OsPHGPx are lost in a highly cooperative single transition.The unfolding process comprises of three zones:the native base-line zone between 0 and 2.5 mol/L urea,the transition zone between 2.5 and 5.5 mol/L urea,and the denatured base-line zone above 5.5 mol/L urea.The transition zone has a midpoint at about 4.0 mol/L urea.
基金supported by the National Natural Science Foundation of China(11274374)the National BasicResearch Program of China(2009CB930704)
文摘Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin have already been investigated.However,the conformation transitions induced by cisplatin are not clear.In the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM imaging.We observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod structures.We found that the formation of micro-rod structures depends on the DNA sequence.Based on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.
文摘Much attention has been paid to the natural mechanism of silkworm spinning due to the impressive me-chanical properties of the natural fibers. In this work, we studied the effect of Cu(II) ions on the secondary structure of Bombyx mori regenerated silk fibroin (SF) in dilute solution by circular dichroism (CD). The results indicate that a given amount of Cu(II) induces the SF conformational transition from random coil to β-sheet, however, further addition of Cu(II) is unfavorable for this conversion. Meanwhile, the conformational changes induced by Cu(II) follow a nuclea-tion-dependent aggregation mechanism, which is similar to that found in Prion protein (PrP) denaturation and Aβ-pep- tide aggregations, leading to the neurodegenerative disease. This work would help one understand further the natural spinning process of silkworm. Additionally, it would be sig-nificant for the study of the nervous system diseases, because silk fibroin, extracted in large amounts from Bombyx mori silkworm gland, could be a proper model to study PrP dena-turation and Aβ-peptide aggregations.
