7bc6: Difference between revisions
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==Cryo-EM structure of the outward open proton coupled folate transporter at pH 7.5== | |||
<StructureSection load='7bc6' size='340' side='right'caption='[[7bc6]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7bc6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BC6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7bc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bc6 OCA], [https://pdbe.org/7bc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bc6 RCSB], [https://www.ebi.ac.uk/pdbsum/7bc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bc6 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:34040256</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7bc6" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Gallus gallus]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Deme JC]] | |||
[[Category: Lea SM]] | |||
[[Category: Newstead S]] | |||
[[Category: Parker JL]] | |||
Latest revision as of 11:36, 17 October 2024
Cryo-EM structure of the outward open proton coupled folate transporter at pH 7.5Cryo-EM structure of the outward open proton coupled folate transporter at pH 7.5
Structural highlights
Publication Abstract from PubMedFolates (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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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