8t6u - Revision history

OCA at 11:23, 14 March 2024

OCA — Thu, 14 Mar 2024 11:23:42 GMT

←Older revision		Revision as of 11:23, 14 March 2024
Line 12:		Line 12:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN] Band 3 is the major integral glycoprotein of the erythrocyte membrane. Band 3 has two functional domains. Its integral domain mediates a 1:1 exchange of inorganic anions across the membrane, whereas its cytoplasmic domain provides binding sites for cytoskeletal proteins, glycolytic enzymes, and hemoglobin.		[https://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN] Band 3 is the major integral glycoprotein of the erythrocyte membrane. Band 3 has two functional domains. Its integral domain mediates a 1:1 exchange of inorganic anions across the membrane, whereas its cytoplasmic domain provides binding sites for cytoskeletal proteins, glycolytic enzymes, and hemoglobin.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Anion exchanger 1 (AE1), a member of the solute carrier (SLC) family, is the primary bicarbonate transporter in erythrocytes, regulating pH levels and CO(2) transport between lungs and tissues. Previous studies characterized its role in erythrocyte structure and provided insight into transport regulation. However, key questions remain regarding substrate binding and transport, mechanisms of drug inhibition and modulation by membrane components. Here we present seven cryo-EM structures in apo, bicarbonate-bound and inhibitor-bound states. These, combined with uptake and computational studies, reveal important molecular features of substrate recognition and transport, and illuminate sterol binding sites, to elucidate distinct inhibitory mechanisms of research chemicals and prescription drugs. We further probe the substrate binding site via structure-based ligand screening, identifying an AE1 inhibitor. Together, our findings provide insight into mechanisms of solute carrier transport and inhibition.

-	Substrate binding and inhibition of the anion exchanger 1 transporter.,Capper MJ, Yang S, Stone AC, Vatansever S, Zilberg G, Mathiharan YK, Habib R, Hutchinson K, Zhao Y, Schlessinger A, Mezei M, Osman R, Zhang B, Wacker D Nat Struct Mol Biol. 2023 Sep 7. doi: 10.1038/s41594-023-01085-6. PMID:37679563<ref>PMID:37679563</ref>	+	==See Also==
-		+	*[[Anion exchange protein 3D structures\|Anion exchange protein 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 8t6u" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:19, 20 September 2023

OCA — Wed, 20 Sep 2023 18:19:53 GMT

←Older revision		Revision as of 18:19, 20 September 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8t6u is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Cryo-EM structure of human Anion Exchanger 1 bound to Dipyridamole==
		+	<StructureSection load='8t6u' size='340' side='right'caption='[[8t6u]], [[Resolution\|resolution]] 3.13Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8t6u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8T6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8T6U 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]] 3.13Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=H9F:2-[[2-[bis(2-hydroxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol'>H9F</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene></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=8t6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8t6u OCA], [https://pdbe.org/8t6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8t6u RCSB], [https://www.ebi.ac.uk/pdbsum/8t6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8t6u ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN] Defects in SLC4A1 are the cause of elliptocytosis type 4 (EL4) [MIM:[https://omim.org/entry/109270 109270]. EL4 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.<ref>PMID:1722314</ref> <ref>PMID:1538405</ref> Defects in SLC4A1 are the cause of spherocytosis type 4 (SPH4) [MIM:[https://omim.org/entry/612653 612653]; also known as hereditary spherocytosis type 4 (HS4). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal.<ref>PMID:8547122</ref> <ref>PMID:1378323</ref> <ref>PMID:7530501</ref> <ref>PMID:8943874</ref> <ref>PMID:8640229</ref> <ref>PMID:9207478</ref> <ref>PMID:9012689</ref> <ref>PMID:9233560</ref> <ref>PMID:9973643</ref> <ref>PMID:10580570</ref> <ref>PMID:10942416</ref> <ref>PMID:10745622</ref> <ref>PMID:11380459</ref> <ref>PMID:15813913</ref> <ref>PMID:16227998</ref> Defects in SLC4A1 are the cause of renal tubular acidosis, distal, autosomal dominant (AD-dRTA) [MIM:[https://omim.org/entry/179800 179800]. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with hemolytic anemia (dRTA-HA) [MIM:[https://omim.org/entry/611590 611590]. A disease characterized by the association of hemolytic anemia with distal renal tubular acidosis, the reduced ability to acidify urine resulting in variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with normal red cell morphology (dRTA-NRC) [MIM:[https://omim.org/entry/611590 611590]. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN] Band 3 is the major integral glycoprotein of the erythrocyte membrane. Band 3 has two functional domains. Its integral domain mediates a 1:1 exchange of inorganic anions across the membrane, whereas its cytoplasmic domain provides binding sites for cytoskeletal proteins, glycolytic enzymes, and hemoglobin.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Anion exchanger 1 (AE1), a member of the solute carrier (SLC) family, is the primary bicarbonate transporter in erythrocytes, regulating pH levels and CO(2) transport between lungs and tissues. Previous studies characterized its role in erythrocyte structure and provided insight into transport regulation. However, key questions remain regarding substrate binding and transport, mechanisms of drug inhibition and modulation by membrane components. Here we present seven cryo-EM structures in apo, bicarbonate-bound and inhibitor-bound states. These, combined with uptake and computational studies, reveal important molecular features of substrate recognition and transport, and illuminate sterol binding sites, to elucidate distinct inhibitory mechanisms of research chemicals and prescription drugs. We further probe the substrate binding site via structure-based ligand screening, identifying an AE1 inhibitor. Together, our findings provide insight into mechanisms of solute carrier transport and inhibition.

-	~~Authors~~:	+	Substrate binding and inhibition of the anion exchanger 1 transporter.,Capper MJ, Yang S, Stone AC, Vatansever S, Zilberg G, Mathiharan YK, Habib R, Hutchinson K, Zhao Y, Schlessinger A, Mezei M, Osman R, Zhang B, Wacker D Nat Struct Mol Biol. 2023 Sep 7. doi: 10.1038/s41594-023-01085-6. PMID:37679563<ref>PMID:37679563</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8t6u" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Capper MJ]]
		+	[[Category: Mathiharan YK]]
		+	[[Category: Stone AC]]
		+	[[Category: Wacker D]]
		+	[[Category: Yang S]]
		+	[[Category: Zilberg G]]

OCA at 04:38, 6 September 2023

OCA — Wed, 06 Sep 2023 04:38:17 GMT

←Older revision		Revision as of 04:38, 6 September 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8t6u is ON HOLD	+	The entry 8t6u is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8t6u" [edit=sysop:move=sysop]

OCA — Wed, 28 Jun 2023 20:04:20 GMT

Protected "8t6u" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:04, 28 June 2023

OCA: New page: '''Unreleased structure''' The entry 8t6u is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 28 Jun 2023 20:04:19 GMT

New page: '''Unreleased structure''' The entry 8t6u is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8t6u is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]