7bc6

Cryo-EM structure of the outward open proton coupled folate transporter at pH 7.5

spinqualitylabelsall models 7bc6, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bc6 is a 2 chain structure with sequence from Gallus gallus and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S-adenylsmethionine(1,2). Folate deficiency is associated with a number of developmental, immune and neurological disorders(3-5). Mammals cannot synthesize folates de novo; several systems have therefore evolved to take up folates from the diet and distribute them within the body(3,6). The proton-coupled folate transporter (PCFT) (also known as SLC46A1) mediates folate uptake across the intestinal brush border membrane and the choroid plexus(4,7), and is an important route for the delivery of antifolate drugs in cancer chemotherapy(8-10). How PCFT recognizes folates or antifolate agents is currently unclear. Here we present cryo-electron microscopy structures of PCFT in a substrate-free state and in complex with a new-generation antifolate drug (pemetrexed). Our results provide a structural basis for understanding antifolate recognition and provide insights into the pH-regulated mechanism of folate transport mediated by PCFT. Structural basis of antifolate recognition and transport by PCFT.,Parker JL, Deme JC, Kuteyi G, Wu Z, Huo J, Goldman ID, Owens RJ, Biggin PC, Lea SM, Newstead S Nature. 2021 Jul;595(7865):130-134. doi: 10.1038/s41586-021-03579-z. Epub 2021 , May 26. PMID:34040256 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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