OCA at 08:59, 29 September 2021

OCA — Wed, 29 Sep 2021 08:59:54 GMT

←Older revision		Revision as of 08:59, 29 September 2021
Line 1:		Line 1:

	==ASCT2 in the presence of the inhibitor ERA-21 in the outward-open conformation.==		==ASCT2 in the presence of the inhibitor ERA-21 in the outward-open conformation.==
-	<StructureSection load='7bct' size='340' side='right'caption='[[7bct]]' scene=''>	+	<StructureSection load='7bct' size='340' side='right'caption='[[7bct]], [[Resolution\|resolution]] 3.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>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>	+	<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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7bct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bct OCA], [https://pdbe.org/7bct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bct RCSB], [https://www.ebi.ac.uk/pdbsum/7bct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bct ProSAT]</span></td></tr>	+	</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>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7bct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bct OCA], [https://pdbe.org/7bct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bct RCSB], [https://www.ebi.ac.uk/pdbsum/7bct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bct ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7bct" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bonomi M]]	+	[[Category: Bonomi, M]]
-	[[Category: Garaeva AA]]	+	[[Category: Garaeva, A A]]
-	[[Category: Garibsingh RA]]	+	[[Category: Garibsingh, R A]]
-	[[Category: Grewer C]]	+	[[Category: Grewer, C]]
-	[[Category: Ndaru E]]	+	[[Category: Ndaru, E]]
-	[[Category: Paulino C]]	+	[[Category: Paulino, C]]
-	[[Category: Schlessinger A]]	+	[[Category: Schlessinger, A]]
-	[[Category: Shi Y]]	+	[[Category: Shi, Y]]
-	[[Category: Slotboom DJ]]	+	[[Category: Slotboom, D J]]
-	[[Category: Zielewicz L]]	+	[[Category: Zielewicz, L]]
		+	[[Category: Cancer metabolism]]
		+	[[Category: Cryo-em]]
		+	[[Category: Glutamine deprivation]]
		+	[[Category: Homology modeling]]
		+	[[Category: Membrane protein]]
		+	[[Category: Solute carrier transporter]]

OCA at 06:48, 22 September 2021

OCA — Wed, 22 Sep 2021 06:48:30 GMT

←Older revision		Revision as of 06:48, 22 September 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7bct is ~~ON HOLD until Paper Publication~~	+	==ASCT2 in the presence of the inhibitor ERA-21 in the outward-open conformation.==
-		+	<StructureSection load='7bct' size='340' side='right'caption='[[7bct]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>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>
-	~~Description~~:	+	</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=7bct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bct OCA], [https://pdbe.org/7bct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bct RCSB], [https://www.ebi.ac.uk/pdbsum/7bct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bct ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bonomi M]]
		+	[[Category: Garaeva AA]]
		+	[[Category: Garibsingh RA]]
		+	[[Category: Grewer C]]
		+	[[Category: Ndaru E]]
		+	[[Category: Paulino C]]
		+	[[Category: Schlessinger A]]
		+	[[Category: Shi Y]]
		+	[[Category: Slotboom DJ]]
		+	[[Category: Zielewicz L]]

OCA at 06:36, 20 January 2021

OCA — Wed, 20 Jan 2021 06:36:10 GMT

←Older revision		Revision as of 06:36, 20 January 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7bct is ON HOLD	+	The entry 7bct is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7bct" [edit=sysop:move=sysop]

OCA — Wed, 30 Dec 2020 05:16:41 GMT

Protected "7bct" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:16, 30 December 2020

OCA: New page: '''Unreleased structure''' The entry 7bct is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 30 Dec 2020 05:16:40 GMT

New page: '''Unreleased structure''' The entry 7bct is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7bct is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7bct - Revision history

OCA at 08:59, 29 September 2021

OCA at 06:48, 22 September 2021

OCA at 06:36, 20 January 2021

OCA: Protected "7bct" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7bct is ON HOLD Authors: Description: Category: Unreleased Structures