Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27082870.
- Also identified by DOI 10.1371/journal.pone.0153669 and PMC identifier 4833397.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The immunosuppressive drug cyclosporin A (CsA) binds to its receptor protein cyclophilin 18 (Cyp18) in two distinct kinetic phases, while the mechanism remains elusive. Stopped-flow measurements coupled with titration and competition experiments were used to investigate the puzzling two-phase process of CsA and Cyp18 interaction. This study leads to the dissection of different conformational fractions of either direct fast binding or slow binding with rate-limiting conformational inter-conversion and the real-time measurement of kon value (8.34 ± 0.22 x106 M-1s-1) in solution. Furthermore, our study indicates that the structure of CsA during dissociation from the protein possesses a distribution of conformations different from those in solution under equilibrium condition.
Medical subject headings
- Cyclophilins
- Cyclosporine