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Interpretation of Seemingly Contradictory Data: Low NMR S 2 Order Parameters Observed in Helices and High NMR S 2 Order Parameters in Disordered Loops of the Protein hGH at Low pH
Author(s) -
Smith Lorna J.,
Athill Roya,
van Gunsteren Wilfred F.,
Hansen Niels
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700896
Subject(s) - side chain , hydrogen bond , crystallography , order (exchange) , chemistry , nuclear magnetic resonance spectroscopy , stereochemistry , molecule , polymer , organic chemistry , finance , economics
At low pH, human growth hormone (hGH) adopts a partially folded state, in which the native helices are maintained, but the long loop regions and side‐chain packing become disordered. Some of the S 2 order parameters for backbone N−H vectors derived from NMR relaxation measurements on hGH at low pH initially seem contradictory. Three isolated residues (15, 20, and 171) in helices A and D exhibit low order parameter values (<0.5) indicating flexibility, whereas residue 143 in the centre of a long flexible loop region has a high order parameter (0.82). Using S 2 order parameter restraining MD simulations, this paradox has been resolved. Low S 2 values in helices are due to the presence of a mixture of 3 10 ‐helical and α‐helical hydrogen bonds. High S 2 values in relatively disordered parts of a protein may be due to fluctuating networks of hydrogen bonds between the backbone and the side chains, which restrict the motion of N−H bond vectors.