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Solution structure of a unique C5a semi‐synthetic antagonist: Implications in receptor binding
Author(s) -
Zhang Xiaolu,
Boyar William,
Gonnella Nina C.,
Galakatos Nicholas
Publication year - 1997
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560060107
Subject(s) - antiparallel (mathematics) , antagonist , competitive antagonist , stereochemistry , protein tertiary structure , chemistry , receptor , crystallography , biophysics , biochemistry , biology , physics , quantum mechanics , magnetic field
The tertiary structure of a unique C5a receptor antagonist was determined by two‐dimensional NMR spectroscopy. The core domain of this 8‐kDa antagonist exists as an antiparallel helical bundle, similar to recombinant human (rh)‐C5a. However, unlike C5a, the antagonist's C terminus was found to be conformationally restricted along a groove between helices one and four in the core domain. This conformational restriction situates C‐terminal D‐Arg 75 in a wedge between core residues Arg 46 and His 15. Correlation of the antagonist's tertiary structure with point mutation analysis revealed the formation of a positively charged contiguous contact surface comprised of D‐Arg 75, Arg 46, Lys 49, and His 15. The significance of this surface in generating antagonist properties implies a single binding site with the C5a receptor and provides a structural template for drug design.