TEMPOL spin-label has been used to identify surface exposure of protein nuclei from NMR analysis of the induced paramagnetic relaxation enhancements (PRE). The absence of linear dependence between atom depths and observed PRE reveals that specific mechanisms drive the approach of the paramagnet to the protein surface. RNase A represents a unique protein system to explore the fine details of the information offered by TEMPOL induced PRE, due to the abundance of previous results, obtained in solution and in the crystal, dealing with surface dynamics behavior of this protein. MD simulations in explicit solvent have been performed, also in the presence of TEMPOL, in order to delineate the role of intermolecular hydrogen bonds (HB) on PRE extents. Comparison of our results with the ones obtained from multiple solvent crystal structure (MSCS) studies yields information on the specificities that these two techniques have for characterizing protein-ligand interactions, a fundamental step in the development of reliable surface druggability predictors. (C) 2016 Elsevier B.V. All rights reserved.

Niccolai, N., Morandi, E., Gardini, S., Costabile, V., Spadaccini, R., Crescenzi, O., et al. (2017). Hot spot mapping of protein surfaces with TEMPOL: Bovine pancreatic RNase A as a model system. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 1865(2), 201-207 [10.1016/j.bbapap.2016.11.014].

Hot spot mapping of protein surfaces with TEMPOL: Bovine pancreatic RNase A as a model system

Niccolai, Neri;Morandi, Edoardo;Gardini, Simone;Spiga, Ottavia;Bernini, Andrea
2017-01-01

Abstract

TEMPOL spin-label has been used to identify surface exposure of protein nuclei from NMR analysis of the induced paramagnetic relaxation enhancements (PRE). The absence of linear dependence between atom depths and observed PRE reveals that specific mechanisms drive the approach of the paramagnet to the protein surface. RNase A represents a unique protein system to explore the fine details of the information offered by TEMPOL induced PRE, due to the abundance of previous results, obtained in solution and in the crystal, dealing with surface dynamics behavior of this protein. MD simulations in explicit solvent have been performed, also in the presence of TEMPOL, in order to delineate the role of intermolecular hydrogen bonds (HB) on PRE extents. Comparison of our results with the ones obtained from multiple solvent crystal structure (MSCS) studies yields information on the specificities that these two techniques have for characterizing protein-ligand interactions, a fundamental step in the development of reliable surface druggability predictors. (C) 2016 Elsevier B.V. All rights reserved.
2017
Niccolai, N., Morandi, E., Gardini, S., Costabile, V., Spadaccini, R., Crescenzi, O., et al. (2017). Hot spot mapping of protein surfaces with TEMPOL: Bovine pancreatic RNase A as a model system. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 1865(2), 201-207 [10.1016/j.bbapap.2016.11.014].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1233675
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo