Structural Basis for Oxidized Glutathione Recognition by the Yeast Cadmium Factor 1.
| Autor: | Soong TH; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA., Hotze C; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA., Khandelwal NK; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.; Department of Biochemistry and Physics, University of California San Francisco, San Francisco, CA 94158, USA., Tomasiak TM; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 26. Date of Electronic Publication: 2024 Mar 26. |
| DOI: | 10.1101/2024.01.31.578287 |
| Abstrakt: | Transporters from the ABCC family have an essential role in detoxifying electrophilic compounds including metals, drugs, and lipids, often through conjugation with glutathione complexes. The Yeast Cadmium Factor 1 (Ycf1) transports glutathione alone as well as glutathione conjugated to toxic heavy metals including Cd 2+ , Hg 2+ , and As 3+ . To understand the complicated selectivity and promiscuity of heavy metal substrate binding, we determined the cryo-EM structure of Ycf1 bound to the substrate, oxidized glutathione. We systematically tested binding determinants with cellular survival assays against cadmium to determine how the substrate site accommodates different-sized metal complexes. We identify a "flex-pocket" for substrate binding that binds glutathione complexes asymmetrically and flexes to accommodate different size complexes. Competing Interests: Competing Interest Statement: No competing interests are declared |
| Databáze: | MEDLINE |
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