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Title

Identification and characterization of a cyclosporin binding cyclophillin from Staphylococcus aureus
Newman

 

Authors

Soumitra Polley1, Soham Seal1, Avisek Mahapa2, Biswanath Jana1, Anindya Biswas1, Sukhendu Mandal1, Debabrata Sinha1, Keya Sau2 and Subrata Sau1*

 

Affiliation

1Department of Biochemistry, Bose Institute, Kolkata, West Bengal, India; 2Department of Biotechnology, Haldia Institute of Technology, Haldia, West Bengal, India;

 

Email

subratasau@gmail.com

 

Article Type

Hypothesis

 

Date

Received December 28, 2016; Accepted February 4, 2017; Published March 31, 2017

 

Abstract

Cyclophilins, a class of peptidyl-prolyl cis-trans isomerase (PPIase) enzymes, are inhibited by cyclosporin A (CsA), an immunosuppressive drug. Staphylococcus aureus Newman, a pathogenic bacterium, carries a gene for encoding a putative cyclophilin (SaCyp). SaCyp shows significant homology with other cyclophilins at the sequence level. A three-dimensional model structure of
SaCyp harbors a binding site for CsA. To verify whether SaCyp possess both the PPIase activity and the CsA binding ability, we have purified and investigated a recombinant SaCyp (rCyp) using various in vitro tools. Our RNase T1 refolding assay indicates that rCyp has a substantial extent of PPIase activity. rCyp that exists as a monomer in the aqueous solution is truly a cyclophilin as its catalytic
activity specifically shows sensitivity to CsA. rCyp appears to bind CsA with a reasonably high affinity. Additional investigations reveal that binding of CsA to rCyp alters its structure and shape to some extent. Both rCyp and rCyp-CsA are unfolded via the formation of at least one intermediate in the presence of guanidine hydrochloride. Unfolding study also indicates that there is substantial extent of thermodynamic stabilization of rCyp in the presence of CsA as well. The data suggest that rCyp may be exploited to screen the new antimicrobial agents in the future.

 

Keywords

Staphylococcus aureus, cyclophilin, cyclosporin A, GdnCl, unfolding, intermediate, and stability

 

Citation

Polley et al. Bioinformation 13(3): 78-85 (2017)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.