1CFA

Solution structure of a unique C5a semi-synthetic antagonist: implications in receptor binding.

(1997) Protein Sci 6: 65-72

• PubMed: 9007977 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1002/pro.5560060107
• Primary Citation of Related Structures:  
  1CFA


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Ciba-Geigy Corporation, Pharmaceuticals Division, Summit, New Jersey 07901, USA.