1,721,086 research outputs found
Protein surface accessibility probed by solvent and paramagnetic molecules
No full textProteins very unlikely interact randomly with their molecular environment. Water, the most ubiquitous and abundant molecule of life, certainly plays a major role in controlling the intermolecular dialog of proteins. Thus, understanding how proteins drive other molecules to specific surface regions to trigger the biological function should imply a preliminary accurate delineation of protein hydration. Afterwards, the way a given protein surface region becomes a binding site, through particular surface shape, amino acid composition and topology, could be investigated by probing the protein surface accessibility to molecules different from water. It is apparent that delineating the mechanisms of protein surface accessibility would be precious to expand the rational basis for designing modified enzymes with modulated activity or protein ligands with biotechnological relevance.
A good wealth of information on protein accessibility has been offered by nuclear magnetic resonance, NMR, through dynamic studies of proteins involved in exchanging and binding processes. Studies on the effects induced by neutral paramagnetic probes on protein NMR signals have been proved to be of particular relevance in delineating the complex dynamics occurring at the protein-solvent interface.
The fact that paramagnetic probes might be involved in biased approaches towards a protein surface, due to their affinity with specific amino acid side chains or structural determinants, has been considered and several EPR studies have confirmed that preferential interactions between TEMPOL and proteins hardly occur. Furthermore, for the typical neutral or anionic Gd(III) chelates currently used as MRI contrast agents no evidence has been found by relaxometric techniques of weak interaction with specific molecular sites, even in the crowded molecular environments typical of biological fluids.
The way surface patches of several protein systems are accessible to TEMPOL, GdDTPA-BMA and Gd2L7, a newly designed probe, is here reviewed. The fact that, irrespective of size and chemical nature of the three used paramagnets, a common path for their approach to the protein surface can be observed, is of primary importance. This finding suggested that uneven mobility of solvent molecules near to the protein surface could determine preferential access to protein regions where water molecule diffusion is particularly fast. A combined analysis of data obtained from Molecular Dynamics simulations and ePHOGSY spectra seems to confirm complementarity between hydrated surface sites and paramagnet accessible regions of all the proteins which we have investigated so far
Spatial Structure By 1d and 2d Nuclear-relaxation Methods
No full textA detailed conformational investigation of Active Site Peptides (ASP) in solution can be performed for defining the steric aspects of the biological function and for obtaining the structural base for a rational design of new drugs and vaccines. Nuclear Overhauser Effects (NOE) from 1D and 2D spectra and spin-lattice relaxation rates are the main tools for determining internuclear distances and molecular dynamics of ASP. For these molecular systems, the structural analysis of relaxation data is not always straightforward, since multiple conformational equilibria and/or Brownian motions that are intermediate in the NMR time scale may yield undetectable NOEs
Determination of Heteronuclear Dipolar Contributions To Proton Spin-lattice Relaxation Induced By Low Abundant Nuclei
No full textProton Detection of Heteronuclear Dipolar Couplings
No full textA method is proposed for the calculation of heteronuclear dipolar coupling between two 1/2 nuclei, X and Y, by measuring the spin-lattice relaxation rates of the abundant Y nucleus and of the satellite peaks (1H, 31P, 19F) due to the scalar coupling of Y with the less abundant X nucleus. The 1H-13C dipolar interaction has been evaluated from the proton spin-lattice relaxation rates of tyrosine in water solution and the effective correlation times of the aromatic moiety have been calculated
FT-NMR and EPR relaxation studies of inner- and outer- sphere complexes of the Mn(II) paramagnetic probe
No full textModello molecolare tridimensionale del peplomero del coronavirus della SARS come base razionale per la progettazione di farmaci e kit diagnostici
No full textMechanism of exchange in the MnII-ATP system from fourier transform nuclear magnetic resonance and electron paramagnetic resonance data
No full textNuclear spin relaxation studies have been performed on the Mn II-ATP system. Longitudinal and transverse relaxation times of water protons have been measured and their dependence upon the concentration of the ligand 5′-ATP has been investigated. Temperature and pH effects on both electron and nuclear relaxation rates have been analysed and discussed
Proton spin-lattice relaxation studies of [D-Ala2-Met5]enkephalin
No full textApplication of selective and nonselective proton relaxation rate measurements to molecules outside the ω02tc2 « 1 limit is explored using [D-Ala2-Met5]enkephalin. Monoselective, biselective, and nonselective measurements yielded cross-relaxation rates, σ, and F ratios; from these, it was deduced that enkephalin has a relatively rigid backbone, internal motion of the Ala2, Phe4, and Met5 side chains, a small reorientation of the Tyr1 aromatic ring, and proximity of the Ala2 and Met5 methyl groups. These data support but do not prove the existence of the β-turn conformations. All proton relaxation is dominated by dipolar mechanisms. © 1980, American Chemical Society. All rights reserved
1H-NMR relaxation investigation of water bound to bovine rod outer segment disk membranes
No full textSpin-lattice relaxation times T(1) in deuterated aqueous dispersions of lecithin and rod outer segment disk membranes were measured at various concentrations and temperatures. Fast chemical exchange between two loosely defined phases of water molecules was shown to fit the data, allowing the dynamic features of "bound" water and the hydration of the biological membrane to be evaluated. The state of the water was shown to be also involved in vision physiology
Carbon and Proton Nuclear Magnetic-relaxation Study of Thymidine Thymidine Interaction In Solution
No full textThe nucleoside thymidine has been used as a model system to study the effects of the presence of intra- and intermolecular interactions on both carbon spin-lattice relaxation rates R1 and selective {Ha}C nuclear Overhauser effects (NOEs). The carbon R1 analysis permits the determination of the correlation times of each moiety of thymidine. These findings, and a careful analysis of the selective {Ha}C NOEs, point out the presence of a dimeric complex in solution in which stacking and hydrogen-bond interactions play an important role in the stabilization of this structure. Moreover, the effect induced on selective {Ha}C NOEs by the presaturation of exchangeable protons has been considered and a method to resolve this problem proposed. © 1987 American Chemical Society
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