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Polley S, Seal S, Mahapa A, et al. Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman. Bioinformation. 2017;13(3):78-85doi: 10.6026/97320630013078.
Polley, S., Seal, S., Mahapa, A., Jana, B., Biswas, A., Mandal, S., Sinha, D., Sau, K., & Sau, S. (2017). Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman. Bioinformation, 13(3), 78-85. https://doi.org/10.6026/97320630013078
Polley, Soumitra, et al. "Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman." Bioinformation vol. 13,3 (2017): 78-85. doi: https://doi.org/10.6026/97320630013078
Polley S, Seal S, Mahapa A, Jana B, Biswas A, Mandal S, Sinha D, Sau K, Sau S. Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman. Bioinformation. 2017 Mar 31;13(3):78-85. doi: 10.6026/97320630013078. eCollection 2017. PMID: 28584448; PMCID: PMC5450249.
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Bioinformation. 2017 Mar 31;13(3):78-85. doi: 10.6026/97320630013078. eCollection 2017.

Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman.

Bioinformation

Soumitra Polley, Soham Seal, Avisek Mahapa, Biswanath Jana, Anindya Biswas, Sukhendu Mandal, Debabrata Sinha, Keya Sau, Subrata Sau

Affiliations

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

PMID: 28584448 PMCID: PMC5450249 DOI: 10.6026/97320630013078

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 possesses 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: GdnCl; Staphylococcus aureus; cyclophilin; cyclosporin A; intermediate; stability; unfolding

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