The Experts below are selected from a list of 57561 Experts worldwide ranked by ideXlab platform
Emil Alexov - One of the best experts on this subject based on the ideXlab platform.
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in silico investigation of Ph Dependence of prolactin and human growth hormone binding to human prolactin receptor
Communications in Computational Physics, 2013Co-Authors: Lin Wang, Shawn Witham, Zhe Zhang, Lin Li, Michael E Hodsdon, Emil AlexovAbstract:: Experimental data shows that the binding of human prolactin (hPRL) to human prolactin receptor (hPRLr-ECD) is strongly Ph-dependent, while the binding of the same receptor to human growth hormone (hGH) is Ph-independent. Here we carry in silico analysis of the molecular effects causing such a difference and reveal the role of individual amino acids. It is shown that the computational modeling correctly predicts experimentally determined pKa's of histidine residues in an unbound state in the majority of the cases and the Ph-Dependence of the binding free energy. Structural analysis carried in conjunction with calculated Ph-Dependence of the binding revealed that the main reason for Ph-Dependence of the binding of hPRL-hPRLr-ECD is a number of salt- bridges across the interface of the complex, while no salt-bridges are formed in the hGH-hPRlr-ECD. Specifically, most of the salt-bridges involve histidine residues and this is the reason for the Ph-Dependence across a Physiological range of Ph. The analysis not only revealed the molecular mechanism of the Ph-Dependence of the hPRL-hPRLr-ECD, but also provided critical insight into the underlying Physic-chemical mechanism.
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ANISOTROPIC BEHAVIOR OF THE Ph Dependence PART OF YOUNG'S MODULUS IN A LYSOZYME TRICLINIC CRYSTAL
Biopolymers, 1995Co-Authors: Emil Alexov, Boris P. Atanasov, T. UekiAbstract:A numerical simulation of the Young's modulus Ph Dependence in a triclinic crystal of hen egg white lysozyme is performed. On the basis of calculation of electrostatic interactions between the molecules in the crystal at different Ph values, we obtain the Young's modulus quantity as a function of Ph. The analysis is carried out along the main crystal axes as well as along the [011] direction. In the last case, a good agreement between our calculations of Young's modulus Ph Dependence and the experimental data [V. N. Morosov and T. Ya. Morozova (1981) Biopolymers, Vol. 20, pp. 451–467] is obtained. The calculations show a strong anisotropy of both the absolute value of the electrostatic part of Young's modulus and its Ph Dependence along different directions. A detailed analysis of the electrostatic potential inside the crystal, as well as the charged group distribution in the contact areas, permit us to find the reason for the anisotropy. It is caused by a nonuniform distribution of the charged residues in the lysozyme molecule and especially by the titration behavior of certain acidic groups. It is also shown that Young's modulus depends on the ionic strength, being anisotropic. The reason is that the cavities are not uniformly distributed within the crystal. They are located predominantly along the c axis. © 1995 John Wiley & Sons, Inc.
Nobuhiro Ohta - One of the best experts on this subject based on the ideXlab platform.
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Ph Dependence of the fluorescence lifetime of FAD in solution and in cells.
International Journal of Molecular Sciences, 2013Co-Authors: Serajul Islam, Takakazu Nakabayashi, Masataka Kinjo, Masato Honma, Nobuhiro OhtaAbstract:We have studied Physiological parameters in a living cell using fluorescence lifetime imaging of endogenous chromoPhores. In this study, Ph Dependence of the fluorescence lifetime of flavin adenine dinucleotide (FAD), that is a significant cofactor exhibiting autofluorescence, has been investigated in buffer solution and in cells. The fluorescence lifetime of FAD remained unchanged with Ph 5 to 9 in solution. However, the fluorescence lifetime in HeLa cells was found to decrease with increasing intracellular Ph, suggesting that Ph in a single cell can be estimated from the fluorescence lifetime imaging of FAD without adding exogenous fluorescent probes.
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Ph Dependence of the fluorescence lifetime of enhanced yellow fluorescent protein in solution and cells
Journal of Photochemistry and Photobiology A: Chemistry, 2012Co-Authors: Takakazu Nakabayashi, Shugo Oshita, Ryoya Sumikawa, Fan Sun, Masataka Kinjo, Nobuhiro OhtaAbstract:Abstract Ph Dependence of the fluorescence decay profile of enhanced yellow fluorescent protein (EYFP) depends on the excitation wavelength. The correlation between the fluorescence lifetime and Ph in solution is discussed in terms of the acid–base equilibrium of the chromoPhore of EYFP. Fluorescence lifetime images of EYFP in HeLa cells have also been measured at various values of intracellular Ph. A remarkable Ph Dependence of the fluorescence lifetime image is observed in Ph 4.5–6.0, indicating that Ph in a single cell can be evaluated using the fluorescence lifetime image of EYFP especially in the acidic condition.
Giancarlo Marconi - One of the best experts on this subject based on the ideXlab platform.
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Monoelectronic reduction of dihydroartemsisinin (DHA): Ph Dependence and product analysis
Tetrahedron Letters, 2013Co-Authors: Maria Luisa Navacchia, Massimo L. Capobianco, Mila D'angelantonio, Giancarlo MarconiAbstract:Abstract The reaction of dihydroartemisinin (DHA) with solvated electrons ( e solv - ) generated under radiolytic conditions showed high Ph Dependence. The reduction performed under neutral conditions led to the formation of compound P1 deriving from the initial alkoxyl radical as the only detectable product.
Richard Neutze - One of the best experts on this subject based on the ideXlab platform.
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Ph Dependence of Copper Geometry, Reduction Potential, and Nitrite Affinity in Nitrite Reductase
The Journal of biological chemistry, 2006Co-Authors: Frida Jacobson, Arthur M.a. Pistorius, Daniel Farkas, W.j. De Grip, Örjan Hansson, Lennart Sjölin, Richard NeutzeAbstract:Many properties of copper-containing nitrite reductase are Ph-dependent, such as gene expression, enzyme activity, and substrate affinity. Here we use x-ray diffraction to investigate the structural basis for the Ph Dependence of activity and nitrite affinity by examining the type 2 copper site and its immediate surroundings in nitrite reductase from Rhodobacter sPhaeroides 2.4.3. At active Ph the geometry of the substrate-free oxidized type 2 copper site shows a near perfect tetrahedral geometry as defined by the positions of its ligands. At higher Ph values the most favorable copper site geometry is altered toward a more distorted tetrahedral geometry whereby the solvent ligand adopts a position opposite to that of the His-131 ligand. This Ph-dependent variation in type 2 copper site geometry is discussed in light of recent computational results. When co-crystallized with substrate, nitrite is seen to bind in a bidentate fashion with its two oxygen atoms ligating the type 2 copper, overlapping with the positions occupied by the solvent ligand in the high and low Ph structures. Fourier transformation infrared spectroscopy is used to assign the Ph Dependence of the binding of nitrite to the active site, and EPR spectroscopy is used to characterize the Ph Dependence of the reduction potential of the type 2 copper site. Taken together, these spectroscopic and structural observations help to explain the Ph Dependence of nitrite reductase, highlighting the subtle relationship between copper site geometry, nitrite affinity, and enzyme activity.
Julie D. Forman-kay - One of the best experts on this subject based on the ideXlab platform.
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Site-specific contributions to the Ph Dependence of protein stability
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Martin Tollinger, Karin A. Crowhurst, Lewis E. Kay, Julie D. Forman-kayAbstract:Understanding protein stability is a significant challenge requiring characterization of interactions within both folded and unfolded states. Of these, electrostatic interactions influence ionization equilibria of acidic and basic groups and diversify their pKa values. The Ph Dependence of the thermodynamic stability (ΔGFU) of a protein arises as a consequence of differential pKa values between folded and unfolded states. Previous attempts to calculate Ph-dependent contributions to stability have been limited by the lack of experimental unfolded state pKa values. Using recently developed NMR spectroscopic methods, we have determined residue-specific pKa values for a thermodynamically unstable Src homology 3 domain in both states, enabling the calculation of the Ph Dependence of stability based on simple analytical expressions. The calculated Ph stability profile obtained agrees very well with experiment, unlike profiles derived from two current models of electrostatic interactions within unfolded states. Most importantly, per-residue contributions to the Ph Dependence of ΔGFU derived from the data provide insights into specific electrostatic interactions in both the folded and unfolded states and their roles in protein stability. These interactions include a hydrogen bond between the Asp-8 side-chain and the Lys-21 backbone amide group in the folded state, which represents a highly conserved interaction in Src homology 3 domains.
