Cargando…

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

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 othe...

Descripción completa

Detalles Bibliográficos
Autores principales: Polley, Soumitra, Seal, Soham, Mahapa, Avisek, Jana, Biswanath, Biswas, Anindya, Mandal, Sukhendu, Sinha, Debabrata, Sau, Keya, Sau, Subrata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Biomedical Informatics 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450249/
https://www.ncbi.nlm.nih.gov/pubmed/28584448
http://dx.doi.org/10.6026/97320630013078
_version_ 1783239932408496128
author Polley, Soumitra
Seal, Soham
Mahapa, Avisek
Jana, Biswanath
Biswas, Anindya
Mandal, Sukhendu
Sinha, Debabrata
Sau, Keya
Sau, Subrata
author_facet Polley, Soumitra
Seal, Soham
Mahapa, Avisek
Jana, Biswanath
Biswas, Anindya
Mandal, Sukhendu
Sinha, Debabrata
Sau, Keya
Sau, Subrata
author_sort Polley, Soumitra
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5450249
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Biomedical Informatics
record_format MEDLINE/PubMed
spelling pubmed-54502492017-06-05 Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman Polley, Soumitra Seal, Soham Mahapa, Avisek Jana, Biswanath Biswas, Anindya Mandal, Sukhendu Sinha, Debabrata Sau, Keya Sau, Subrata Bioinformation Hypothesis 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. Biomedical Informatics 2017-03-31 /pmc/articles/PMC5450249/ /pubmed/28584448 http://dx.doi.org/10.6026/97320630013078 Text en © 2017 Biomedical Informatics http://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Hypothesis
Polley, Soumitra
Seal, Soham
Mahapa, Avisek
Jana, Biswanath
Biswas, Anindya
Mandal, Sukhendu
Sinha, Debabrata
Sau, Keya
Sau, Subrata
Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman
title Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman
title_full Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman
title_fullStr Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman
title_full_unstemmed Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman
title_short Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman
title_sort identification and characterization of a cyclosporin binding cyclophilin from staphylococcus aureus newman
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450249/
https://www.ncbi.nlm.nih.gov/pubmed/28584448
http://dx.doi.org/10.6026/97320630013078
work_keys_str_mv AT polleysoumitra identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT sealsoham identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT mahapaavisek identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT janabiswanath identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT biswasanindya identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT mandalsukhendu identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT sinhadebabrata identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT saukeya identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman
AT sausubrata identificationandcharacterizationofacyclosporinbindingcyclophilinfromstaphylococcusaureusnewman