Reorientation and Solvation Dynamics of Bulk and Confined Alcohols

Reorientation and solvation dynamics play a central role in chemistry in the liquid phase. In this work, molecular dynamics simulations are used to study hydroxyl group reorientation dynamics for a series of neat linear alcohols. The recently developed extended jump model satisfactorily explains reorientational slowing with increasing chain length for the water/methanol/ethanol series. The analysis indicates that hydrogen bond strength and exchange geometries are similar across the series, and that the dynamic retardation originates with decreased hydrogen bond exchange due to the increased excluded volume associated with longer alkyl chains. The reorientation of intact hydrogen bonds is thus the dominant reorientation pathway in lower alcohols, while hydrogen bond exchange is dominant in water. Simulation data for higher alcohols show emergent timescales and increased ordering in the liquid, which can also be interpreted within the extended jump model. While new barriers, which are the origin of the additional timescales, appear in free energy profiles for reorientation, solvent viscosity must also be considered. Ethanol and a Stockmayer model solute were confined within a roughly cylindrical silica pore to investigate the effect of confinement on solvation dynamics. The results of solute free energy calculations along a one-dimensional cut through the pore indicate that the charge distribution of the solute controls its location within the pore. Furthermore, the fluorescence energy is a function of solute position in a hydrophilic (but not hydrophobic) pore. These effects originate from silica surface roughness and chemistry, which also strongly alter solvent behavior in the pore. The results indicate that solute motion contributes to the time-dependent fluorescence (TDF) spectrum, but the extent to which this can be observed is still under investigation. A comparison of TDF spectra and other solute properties in the pore for the Stockmayer solute and coumarin 153 dye model indicate that identifying how specific solute and silica properties combine to change spectral properties will require systematic testing of a series of dye and confinement models

Enzyme Activity of Phosphatase of Regenerating Liver (PRL-1) Is Controlled by Redox Environment and Its C-terminal Residues

This publication was made possible by National Institutes of Health Grant P20 RR-17708 from the National Center for Research Resources and the Kansas University Center for Research. This work was additionally supported by fellowships for A.L.S. from Amgen and the Edith and Eleta Ernst Cancer Research Fellowship. The Q-Tof2tm instrument was purchased with support from KSTAR, Kansas-administered NSF EPSCoR, and the University of Kansas. The CapXL HPLC system was obtained with support from KCALSI.Phosphatase of regenerating liver-1 (PRL-1) belongs to a unique subfamily of protein tyrosine phosphatases (PTPases) associated with oncogenic and metastatic phenotypes. While considerable evidence exists to supports a role for PRL-1 in promoting proliferation, the biological regulators and effectors of PRL-1 activity remain unknown. PRL-1 activity is inhibited by disulfide bond formation at the active site in vitro, suggesting PRL-1 may be susceptible to redox regulation in vivo. Because PRL-1 has been observed to localize to several different subcellular locations and cellular redox conditions vary with tissue type, age, stage of cell cycle and subcellular location, we determined the reduction potential of the active site disulfide bond that controls phosphatase activity to better understand the function of PRL-1 in various cellular environments. We used high-resolution solution NMR spectroscopy to measure the potential and found it to be −364.3 ± 1.5 mV. Because normal cellular environments range from −170 to −320 mV, we concluded that nascent PRL-1 would be primarily oxidized inside cells. Our studies show that a significant conformational change accompanies activation, suggesting a post-translational modification may alter the reduction potential, conferring activity. We further demonstrate that alteration of the C-terminus renders the protein reduced and active in vitro, implying the C-terminus is an important regulator of PRL-1 function. These data provide a basis for understanding how subcellular localization regulates the activity of PRL-1 and, with further investigation, may help reveal how PRL-1 promotes unique outcomes in different cellular systems, including proliferation in both normal and diseased states