关键词：
Protein disulfide isomerase
P5
Molecular chaperone
Biosensor analysis
Vincristine
Inhibitor
摘要：
Binding of aminoglycoside antibiotics to protein disulfide isomerase (PDI) is known to inhibit the chaperone activity but not the isomerase activity of PDI. The amino sugar moiety of the antibiotics is a key factor in these interactions. In the present study, domain deletion analysis of human PDI (hPDI) revealed that the a'c domain is significant for binding to aminoglycoside antibiotics;however, other domains, including the a, b, and b' domains, are also required, as assessed using the Biacore biosensor analysis system. It was found that the drug compounds interacting with the hPDI family of proteins can be classified into four groups according to the recognition motif for hPDI and hP5. The anti-cancer drug vincristine was found to inhibit chaperone activity but not isomerase activity for both hPDI and hP5 in vitro. Interestingly, a 100:1 molar ratio of vincristine to hPDI or hP5 was sufficient to almost completely inhibit the chaperone activity of hPDI and hP5. These findings may be useful not only for future structure-function studies of the PDI family of proteins but also for new drug design, since PDI plays a critical role in protein-folding in the endoplasmic reticulum and is indispensable for cell viability. (c) 2008 Published by Elsevier Ltd.
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中文科技期刊
