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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mao, Xuming Chen, Zhigang Wang, Wei Li, Yongquan Guan, Wenjun Guo, Xiaoxian Li, Jingkai Chen, Xinyu |
| Description | Author Affiliation: Chen Z ( Zhejiang University, College of Life Sciences, Hangzhou, China.); Li J ( Zhejiang University, College of Life Sciences, Hangzhou, China.); Wang W ( Zhejiang University, College of Life Sciences, Hangzhou, China.); Guo X ( Cornell University, Division of Nutritional Sciences, Ithaca, NY, USA.); Li Y ( Zhejiang University, College of Life Sciences, Hangzhou, China.); Mao X ( Zhejiang University, College of Life Sciences, Hangzhou, China.); Chen X ( Zhejiang Hospital, Hangzhou, China.); Guan W ( Zhejiang University, College of Life Sciences, Hangzhou, China. Electronic address: guanwj@zju.edu.cn.) |
| Abstract | As a mammalian p-glycoprotein homolog, Pdr5p is a major ATP-binding cassette transporter for cellular detoxification in the yeast Saccharomyces cerevisiae. In this study, two novel loss-of-function mutations located adjacent to the ends of the predicted transmembrane helices of Pdr5p were identified. C793F and S1230L mutations considerably impaired the transport activity of Pdr5p without affecting the ATPase activity and the expression level of the protein. Our results demonstrate that the size of residue 793 and the hydrophobicity of residue 1230 are important for Pdr5p efflux function. It reveals that amino acid residues located near the end of transmembrane helix play an important role in drug efflux of Pdr5p. Molecular docking results further suggest that these two single mutations might have disturbed interactions between the drugs and Pdr5p, preventing the drugs from approaching the intracellular or extracellular portal and subsequently from being exported by Pdr5p. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 3 |
| Volume Number | 1838 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2014-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | ATP-Binding Cassette Transporters Genetics Antifungal Agents Pharmacology Cell Membrane Metabolism Mutation Saccharomyces Cerevisiae Proteins Saccharomyces Cerevisiae Chemistry Antineoplastic Agents Biological Transport Drug Effects Cycloheximide Drug Resistance, Fungal Fluconazole Immunosuppressive Agents Mutagenesis, Site-Directed Rhodamines Tacrolimus Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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