PROBING PROTEIN-STRUCTURE BY SOLVENT PERTURBATION OF NMR-SPECTRA - THE SURFACE ACCESSIBILITY OF BOVINE PANCREATIC TRYPSIN-INHIBITOR

Citation
H. Molinari et al., PROBING PROTEIN-STRUCTURE BY SOLVENT PERTURBATION OF NMR-SPECTRA - THE SURFACE ACCESSIBILITY OF BOVINE PANCREATIC TRYPSIN-INHIBITOR, Biophysical journal, 73(1), 1997, pp. 382-396
Citations number
46
Categorie Soggetti
Biophysics
Journal title
ISSN journal
00063495
Volume
73
Issue
1
Year of publication
1997
Pages
382 - 396
Database
ISI
SICI code
0006-3495(1997)73:1<382:PPBSPO>2.0.ZU;2-5
Abstract
In the absence oi specific interactions, the relative attenuation of p rotein NMR signals due to added stable free radicals such as TEMPOL sh ould reflect the solvent accessibility of the molecular surface, The q uantitative correlation between observed attenuation and surface acces sibility was investigated with a model system, i.e., the small protein bovine pancreatic trypsin inhibitor. A detailed discussion is present ed on the reliability and limits of the approach, and guidelines are p rovided for data acquisition, treatment, and interpretation. The NMR-d erived accessibilities are compared with those obtained from x-ray dif fraction and molecular dynamics data. Although the time-averaged acces sibilities from molecular dynamics are ideally suited to fit the NMR d ata, better agreement was observed between the paramagnetic attenuatio ns of the fingerprint cross-peaks of homonuclear proton spectra and th e total NH and H-alpha accessibilities calculated from x-ray coordinat es, than from time-averaged molecular dynamics simulations. In additio n, the solvent perturbation response appears to be a promising approac h for detecting the thermal conformational evolution of secondary stru cture elements in proteins.