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Updated: Sep 6, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
Published on: May 19, 2016
Structural basis of MRP2 interactions with substrate and inhibitor
Peng Zhao1, Dan-Dan Chen2, Hao-Meng Gao2
1Department of Biophysics, School of Basic Medical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Department of Integration of Chinese and Western Medicine, Peking University, Beijing 100191, China.
Abstract:
MRP2 (ABCC2) contributes to multidrug resistance in cancer treatment and plays a key role in liver detoxification. Recent studies on mammalian MRP2 have elucidated its basic structure and regulation via R-domain phosphorylation and displacement, but have not yet explained its substrate preferences or substrate/inhibitor binding modes. We conducted structural and functional studies on human MRP2 with its substrate SN-38G or inhibitor MK-571. Our research provides structural insight into substrate recognition by MRP2 and the positive cooperativity observed in ATP hydrolysis upon SN-38G stimulation, and reveals structural features that contribute to the recognition of glucuronidated substrates. We further identify an MK-571-associated density within the substrate-binding region rather than the nucleotide-binding sites, although its precise binding mode remains unresolved.
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