Nuclear magnetic resonance studies of the C-terminal human growth hormone fragment I179-C182-[SS]-C189-P191 and the related trisulfide peptide I179-C182-[SSS]-C189-P191.
The synthetic C-terminal hGH fragment I179-C182-[SS]-C189-P191 and the related trisulfide peptide I179-C182-[SSS]-C189-P191 have been studied using homonuclear 1H-NMR methods and distance geometry calculations. The 1H-NMR spectra of both the disulfide (diS) and the trisulfide (triS) were completely assigned. Amide proton exchange rates, NOEs and the temperature dependence of the NH chemical shifts indicate a hydrogen bond in triS between Val185 and Ser188 stabilizing a turn in this region. 3JH,H coupling constants and NOEs were measured and used as input for distance geometry calculations. For triS two families of structures with averaged pairwise backbone root mean square deviations for Cys182-Cys189 of 1.3-1.5 A were found, only one of which is compatible with experimental data. For diS only one family of structures was found, but with such a low structural definition (back bone rmsd > 2 A) that no interpretation into a consensus structure is useful. The generated structures were compared to the crystal structure of the terminal loop in hGH, complexed to its binding proteins. The resemblance was low between the solution structures of the tridecapeptides and the terminal hGH loop.
Strandberg
E
E
Department of Physical Chemistry, Umeå University, Sweden.
Kördel
J
J
Lundin
R
R
Wehler
T
T
Widmalm
G
G
D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D019382:Human Growth Hormone / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry*; D013440:Sulfides / Q000737:chemistry
D010446:Peptide Fragments; D013440:Sulfides; D019382:Human Growth Hormone; D003545:Cysteine