Back
Full-text
Journal article

Interpretation of Seemingly Contradictory Data: Low NMR S2 Order Parameters Observed in Helices and High NMR S2 Order Parameters in Disordered Loops of the Protein hGH at Low pH.

  • Smith LJ Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, South Parks Road, Oxford, OX1 3QR, UK.
  • Athill R Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, South Parks Road, Oxford, OX1 3QR, UK.
  • van Gunsteren WF Laboratory of Physical Chemistry, ETH Zürich, 8093, Zürich, Switzerland.
  • Hansen N Institute of Thermodynamics and Thermal Process Engineering, University of Stuttgart, 70569, Stuttgart, Germany.
Show more…
  • 2017-05-16
Published in:
  • Chemistry (Weinheim an der Bergstrasse, Germany). - 2017
helical structures
human growth hormone
molecular dynamics
order parameters
protein structures
Human Growth Hormone
Humans
Hydrogen Bonding
Hydrogen-Ion Concentration
Magnetic Resonance Spectroscopy
Molecular Dynamics Simulation
Protein Structure, Secondary
English 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 S2 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 S2 order parameter restraining MD simulations, this paradox has been resolved. Low S2 values in helices are due to the presence of a mixture of 310 -helical and α-helical hydrogen bonds. High S2 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://susi.usi.ch/global/documents/254339
Statistics
Document views: 13 File downloads:
  • fulltext.pdf: 0