Skip Navigation


Journal of Biochemistry Advance Access originally published online on May 31, 2008
Journal of Biochemistry 2008 144(3):335-342; doi:10.1093/jb/mvn075
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
144/3/335    most recent
mvn075v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Hashimoto, S.
Right arrow Articles by Imaoka, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hashimoto, S.
Right arrow Articles by Imaoka, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Japanese Biochemical Society

Interaction between Bisphenol Derivatives and Protein Disulphide Isomerase (PDI) and Inhibition of PDI Functions: Requirement of Chemical Structure for Binding to PDI

Shoko Hashimoto, Kazushi Okada* and Susumu Imaoka

Department of Bioscience, Nanobiotechnology Research Center, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan

*To whom correspondence should be addressed. Tel/Fax: +81-79-565-7673, E-mail: bhp46831{at}kwansei.ac.jp

Received April 11, 2008; Accepted May 19, 2008


  Abstract

Bisphenol A (BPA) is an endocrine disrupting chemical and several biological effects have been reported. Previously, protein disulphide isomerase (PDI) was isolated as a target molecule of bisphenol A. In this study, to clarify the effects of BPA on PDI functions, we investigated the relationship between the chemical structure of BPA derivatives and the effects on PDI-mediated isomerase and chaperone activity. We also investigated the effects of changes in the isomerase domain of PDI on the binding of chemicals, using PDI mutants and oxidized or reduced PDI. Among six chemicals, only chemicals, which have a phenol group, can bind to PDI and these chemicals also have an inhibitory effect on PDI-mediated isomerase activity. Changes in the structure of the PDI isomerase domain did not affect chemical-binding activity. On the other hand, the chemicals used in this study have low effects on chaperone activity of PDI. Substitutions in Cys residues (Cys398 and Cys401) of the isomerase active site changed chaperone activity. The present study indicates that phenolic compounds specifically bind to PDI and inhibit isomerase activity. This study provides useful information to predict the biological effects of chemicals and structural studies of PDI containing the function of chemical binding.

Key Words: bisphenol A, protein disulphide isomerase (PDI), dimethyl bisphenol A, chaperone activity, protein folding

Abbreviations: ADH, alcohol dehydrogenase; BPA, Bisphenol A, 2,2-bis(4-hydroxyphenyl)-propane; BPE, Bisphenol E, 1,1-bis(4-hydroxyphenyl)ethane; BPF, Bisphenol F, 4,4-methylenebisphenol; Cumylphenol, 4-{alpha}-Cumylphenol; DMBPA, dimethylbisphenol A, 2,2-bis(4-methoxyphenyl)propane; HIF-1{alpha}, hypoxia-inducible factor-1{alpha}; mBBr, monobromobimane; PDI, protein disulphide isomerase; RNase A, ribonuclease A; T3, 3,3',5-triiodo-L-thyronine


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.