7bct

<table><tr><td colspan='2'>[[7bct]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BCT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BCT FirstGlance]. <br>

</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7bcq|7bcq]], [[7bcs|7bcs]]</div></td></tr>

== Function ==

[[https://www.uniprot.org/uniprot/AAAT_HUMAN AAAT_HUMAN]] Sodium-dependent amino acids transporter that has a broad substrate specificity, with a preference for zwitterionic amino acids. It accepts as substrates all neutral amino acids, including glutamine, asparagine, and branched-chain and aromatic amino acids, and excludes methylated, anionic, and cationic amino acids (PubMed:8702519). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development (PubMed:10708449, PubMed:23492904).<ref>PMID:10708449</ref> <ref>PMID:23492904</ref> <ref>PMID:8702519</ref> (Microbial infection) Acts as a cell surface receptor for Feline endogenous virus RD114.<ref>PMID:10051606</ref> <ref>PMID:10196349</ref> (Microbial infection) Acts as a cell surface receptor for Baboon M7 endogenous virus.<ref>PMID:10196349</ref> (Microbial infection) Acts as a cell surface receptor for type D simian retroviruses.<ref>PMID:10196349</ref>

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== Publication Abstract from PubMed ==

ASCT2 (SLC1A5) is a sodium-dependent neutral amino acid transporter that controls amino acid homeostasis in peripheral tissues. In cancer, ASCT2 is up-regulated where it modulates intracellular glutamine levels, fueling cell proliferation. Nutrient deprivation via ASCT2 inhibition provides a potential strategy for cancer therapy. Here, we rationally designed stereospecific inhibitors exploiting specific subpockets in the substrate binding site using computational modeling and cryo-electron microscopy (cryo-EM). The final structures combined with molecular dynamics simulations reveal multiple pharmacologically relevant conformations in the ASCT2 binding site as well as a previously unknown mechanism of stereospecific inhibition. Furthermore, this integrated analysis guided the design of a series of unique ASCT2 inhibitors. Our results provide a framework for future development of cancer therapeutics targeting nutrient transport via ASCT2, as well as demonstrate the utility of combining computational modeling and cryo-EM for solute carrier ligand discovery.

Rational design of ASCT2 inhibitors using an integrated experimental-computational approach.,Garibsingh RA, Ndaru E, Garaeva AA, Shi Y, Zielewicz L, Zakrepine P, Bonomi M, Slotboom DJ, Paulino C, Grewer C, Schlessinger A Proc Natl Acad Sci U S A. 2021 Sep 14;118(37). pii: 2104093118. doi:, 10.1073/pnas.2104093118. PMID:34507995<ref>PMID:34507995</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Bonomi, M]]

[[Category: Garaeva, A A]]

[[Category: Garibsingh, R A]]

[[Category: Grewer, C]]

[[Category: Ndaru, E]]

[[Category: Paulino, C]]

[[Category: Schlessinger, A]]

[[Category: Shi, Y]]

[[Category: Slotboom, D J]]

[[Category: Zielewicz, L]]

[[Category: Solute carrier transporter]]