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The solution conformations of ferrichrome and deferriferrichrome determined by 1 H‐nmr spectroscopy and computational modeling
Author(s) -
Constantine K. L.,
De Marco A.,
Madrid M.,
Brooks C. L.,
Llinás M.
Publication year - 1990
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360300303
Subject(s) - ferrichrome , chemistry , conformational isomerism , nuclear overhauser effect , nuclear magnetic resonance spectroscopy , crystallography , rubredoxin , molecule , spectroscopy , molecular dynamics , stereochemistry , computational chemistry , two dimensional nuclear magnetic resonance spectroscopy , chemical shift , physics , organic chemistry , biochemistry , escherichia coli , quantum mechanics , bacterial outer membrane , gene
We have applied computational procedures that utilize nmr data to model the solution conformation of ferrichrome, a rigid microbial iron transport cyclohexapeptide of known x‐ray crystallographic structure [D. van der Helm et al. (1980) J. Am. Chem. Soc. 102 , 4224–4231]. The Al 3+ and Ga 3+ diamagnetic analogues, alumichrome and gallichrome, dissolved in d 6 ‐dimethylsulfoxide (d 6 ‐DMSO), were investigated via one‐ and two‐dimensional 1 H‐nmr spectroscopy at 300, 600, and 620 MHz. Interproton distance constraints derived from proton Overhauser experiments were input to a distance geometry algorithm [T. F. Havel and K. Wüthrich (1984) Bull. Math. Biol. 46 , 673–691] in order to generate a family of ferrichrome structures consistent with the experimental data. These models were subsequently optimized through restrained molecular dynamics/energy minimization [B. R. Brooks et al. (1983) J. Comp. Chem. 4 , 187–217]. The resulting structures were characterized in terms of relative energies and conformational properties. Computations based on integration of the generalized Bloch equations for the complete molecule, which include the 14 N‐ 1 H dipolar interaction, demonstrate that the x‐ray coordinates reproduce the experimental nuclear Overhauser effect time courses very well, and indicate that there are no significant differences between the crystalline and solution conformations of ferrichrome. A similar study of the metal free peptide, deferriferrichrome, suggests that at least two conformers are present in d 6 ‐DMSO at 23°C. Both are different from the ferrichrome structure and explain, through conformational averaging, the observed amide NH and C H α multiplet splittings. The occurrence of interconverting peptide backbone conformations yields an increased number of sequential NH‐CH α and NH‐NH Overhauser connectivities, which reflects the 〈 r −6 〉 dependence of the dipolar interaction. Our results support the idea that, in the case of structurally rigid peptides, moderately accurate distance constraints define a conformational subspace encompassing the “true” structure, and that energy considerations reduce the size of this subspace. For flexible peptides, however, the straightforward approach can be misleading since the nmr parameters are averaged over substantially different conformational states.