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PDBsum entry 2k6t
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References listed in PDB file
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Key reference
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Title
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Solution structure of a conformationally restricted fully active derivative of the human relaxin-Like factor.
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Authors
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E.E.Büllesbach,
M.A.Hass,
M.R.Jensen,
D.F.Hansen,
S.M.Kristensen,
C.Schwabe,
J.J.Led.
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Ref.
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Biochemistry, 2008,
47,
13308-13317.
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PubMed id
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Abstract
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Analogous to insulin, the relaxin-like factor (RLF) must undergo a structural
transition to the active form prior to receptor binding. Thus, the C-terminus of
the B chain of RLF folds toward the surface of the central B chain helix,
causing partial obliteration of the two essential RLF receptor-binding site
residues, valine B19 and tryptophan B27. Via comparison of the solution
structure of a fully active C-terminally cross-linked RLF analogue with the
native synthetic human RLF (hRLF), it became clear that the cross-linked
analogue largely retains the essential folding of the native protein. Both
proteins exist in a major and minor conformation, as revealed by multiple
resonances from tryptophan B27 and adjacent residues on the B chain helix.
Notably, the minor conformation is significantly more highly populated in the
chemically cross-linked RLF than it is in the hRLF. In addition, compared to the
unmodified molecule, subtle differences are observed within the B chain helix
whereby the cross-linked derivative shows a reduced level of hydrogen bonding
and significant peak broadening at the binding site residue ValB19. On the basis
of these observations, we suggest that the solution structure of the native
hormone represents an inactive conformer and that a dynamic equilibrium exists
between the C-terminally unfolded binding conformation and the inactive
conformation of the RLF.
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