The Nerve Growth Factor (NGF) neurotrophin acts in the maintenance and growth of neuronal populations. Despite the detailed knowledge of NGF’s role in neuron physiology, the structural and mechanistic determinants of NGF bioactivity modulated by essential endogenous ligands are still lacking. We present the results of an integrated structural and advanced computational approach to characterize the extracellular ATP-NGF interaction. We mapped by NMR the interacting surface and ATP orientation on NGF and revealed the functional role of this interaction in the binding to TrkA and p75NTR receptors by SPR. The role of divalent ions was explored in conjunction with ATP. Our results pinpoint ATP as a likely transient molecular modulator of NGF signaling, in health and disease states.
COBISS.SI-ID: 62353155
F. Merzel is the corresponding author of the article. His contribution to the work was the development of a theoretical model for predicting coating lifetime and degradation. The journal impact factor is 33.23.
COBISS.SI-ID: 6620186
In contrast to the extensive molecular and crystal structure investigations on oxalic acid dihydrate (C2H2O4·2H2O, ?-POX) and its deuterated analogues (?-DOX), stands the absence of a complete vibrational spectra analysis. Such analysis is desirable in view of the proton dynamics in ?-POX crystals. In this communication we report the room temperature polarized IR reflectance spectra of a single crystal of ?-POX recorded from the ac crystal plane, and from the plane containing the b-crystallographic axis, with polarization along the axis. Dispersion analysis of the reflectance spectra of both Bu and Au symmetry type modes, using model dielectric and reflectance function valid for the monoclinic case, have been performed and the results are discussed. Some aspects of the obtained fit results for some of the spectral regions and the peculiar change of the reflectance function with polarization angle are also discussed in this work. A correlation between the crystal structure and measured spectra, together with the results of the performed dispersion analysis, gave answers to some of the problems concerned with the orientation of the transition dipole moments of the IR active modes. The assignment of modes is assisted by DFT calculations. Another aspect covered in this work is the model reflectance functions using different averaging theories that have been applied in obtaining the reflectance spectrum of a polycrystalline sample. The results of the comparison between these spectra and the recorded reflectance spectra from a polycrystalline sample were further discussed.
COBISS.SI-ID: 6594074
Sterol 14[alpha]-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The worldwide increase in the incidence of opportunistic fungal infections and the emerging resistance to available azole-based antifungal drugs, raise the need to develop structurally distinct and selective fungal CYP51 inhibitors. In this work we have, for the first time, investigated the binding of pyridylethanol(phenylethyl)amines to any fungal CYP51. The comparison of the binding to Candida albicans and human CYP51 studied by spectroscopic and modeling methods revealed moieties decisive for selectivity and potency and resulted in the development of highly selective derivatives with significantly increased inhibitory potency. The structure-based insight into the selectivity requirements of this new chemical class of fungal CYP51 inhibitors, their unique binding properties and the low molecular weight of lead derivatives offer novel directions for the targeted development of antifungal clinical candidates.
COBISS.SI-ID: 37513219
IR spectroscopy is a simple and non-destructive tool for battery research. However, its use has been limited due to problems related to the handling of ex situ samples and their interpretation. In this paper, we presented a simple operand ATR IR method, where we used an aluminum bag with two electrodes and an IR permeable silicon window for the cell. The advantages and limitations of the presented method were described on the example of the reaction mechanism of polyanthraquinone in lithium and magnesium organic batteries. We have shown that the intermediate radical anion semikinone is also formed during the reduction process. Continuous measurement of IR spectra also allows the visualization of the gradual accumulation of solid electrolyte interphase at the cathode as a result of discharging and charging the battery.
COBISS.SI-ID: 6689050