Unknown

Dataset Information

0

Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding.


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.

SUBMITTER: Lin W 

PROVIDER: S-EPMC4833397 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

altmetric image

Publications

Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding.

Lin Weilin W   Quintero Andres A   Zhang Yixin Y  

PloS one 20160415 4


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-conversio  ...[more]

Similar Datasets

| S-EPMC4007835 | biostudies-literature
| S-EPMC5450249 | biostudies-literature
| S-EPMC3182837 | biostudies-literature
| S-EPMC4390823 | biostudies-literature
| S-EPMC4822001 | biostudies-literature
| S-EPMC6440624 | biostudies-literature
| S-EPMC9992128 | biostudies-literature
| S-EPMC5511010 | biostudies-literature
| S-EPMC3973219 | biostudies-literature
| S-EPMC4172587 | biostudies-literature