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A Small‐Angle X‐ray Scattering Study of the Binding of Cyclosporin A to Cyclophilin
Author(s) -
Knott R. B.,
Capel M.,
Hansen S.,
Handschumacher R. E.
Publication year - 1995
Publication title -
journal of applied crystallography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.429
H-Index - 162
ISSN - 1600-5767
DOI - 10.1107/s0021889895003268
Subject(s) - small angle x ray scattering , radius of gyration , cyclophilin , crystallography , chemistry , scattering , cyclophilin a , moxalactam , radius , chemical physics , physics , biology , biochemistry , polymer , optics , computer security , antibiotics , organic chemistry , microbiology and biotechnology , computer science , cephalosporin , gene
The small‐angle X‐ray scattering (SAXS) technique was used to investigate structural characteristics of the protein cyclophilin in solution and to attempt to detect major changes induced by the binding of the immunosuppressant drug cyclosporin A. Maximum‐entropy methods were used to analyse the experimental SAXS data. The measured radius of gyration, R g , for cyclophilin is 16.3 (5) Å. This is equivalent to a compact sphere of radius 21.0 Å. There is qualitative agreement between the experimental SAXS profiles and the derived distance‐distribution function, p ( r ), for cyclophilin, and similar profiles calculated from the crystallographic structure. The notable discrepancy is the difference of approximately 1.5 Å in the estimated radius of the equivalent sphere. On binding cyclosporin A, the main structure‐related change in cyclophilin observed under these experimental conditions is an increased propensity to form oligomers. Meaningful estimates of R g for the monomeric complex are not possible because of the presence of a significant population of aggregates. In a second series of experiments, both native cyclophilin and the cyclophilin/cyclosporin A complex readily formed aggregates under the prevailing experimental conditions.