3zux: Difference between revisions
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< | ==Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT.== | ||
<StructureSection load='3zux' size='340' side='right'caption='[[3zux]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3zux]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZUX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=LDA:LAURYL+DIMETHYLAMINE-N-OXIDE'>LDA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene>, <scene name='pdbligand=TCH:TAUROCHOLIC+ACID'>TCH</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=3zux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zux OCA], [https://pdbe.org/3zux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zux RCSB], [https://www.ebi.ac.uk/pdbsum/3zux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zux ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9K0A9_NEIMB Q9K0A9_NEIMB] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
High cholesterol levels greatly increase the risk of cardiovascular disease. About 50 per cent of cholesterol is eliminated from the body by its conversion into bile acids. However, bile acids released from the bile duct are constantly recycled, being reabsorbed in the intestine by the apical sodium-dependent bile acid transporter (ASBT, also known as SLC10A2). It has been shown in animal models that plasma cholesterol levels are considerably lowered by specific inhibitors of ASBT, and ASBT is thus a target for hypercholesterolaemia drugs. Here we report the crystal structure of a bacterial homologue of ASBT from Neisseria meningitidis (ASBT(NM)) at 2.2 A. ASBT(NM) contains two inverted structural repeats of five transmembrane helices. A core domain of six helices harbours two sodium ions, and the remaining four helices pack in a row to form a flat, 'panel'-like domain. Overall, the architecture of the protein is remarkably similar to the sodium/proton antiporter NhaA, despite having no detectable sequence homology. The ASBT(NM) structure was captured with the substrate taurocholate present, bound between the core and panel domains in a large, inward-facing, hydrophobic cavity. Residues near this cavity have been shown to affect the binding of specific inhibitors of human ASBT. The position of the taurocholate molecule, together with the molecular architecture, suggests the rudiments of a possible transport mechanism. | |||
Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT.,Hu NJ, Iwata S, Cameron AD, Drew D Nature. 2011 Oct 5;478(7369):408-11. doi: 10.1038/nature10450. PMID:21976025<ref>PMID:21976025</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3zux" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Symporter 3D structures|Symporter 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[ | |||
== | |||
< | |||
[[Category: Neisseria meningitidis]] | [[Category: Neisseria meningitidis]] | ||
[[Category: Cameron | [[Category: Cameron AD]] | ||
[[Category: Drew | [[Category: Drew D]] | ||
[[Category: Hu | [[Category: Hu N-J]] | ||
[[Category: Iwata | [[Category: Iwata S]] | ||
Latest revision as of 09:00, 19 June 2024
Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT.Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT.
Structural highlights
FunctionPublication Abstract from PubMedHigh cholesterol levels greatly increase the risk of cardiovascular disease. About 50 per cent of cholesterol is eliminated from the body by its conversion into bile acids. However, bile acids released from the bile duct are constantly recycled, being reabsorbed in the intestine by the apical sodium-dependent bile acid transporter (ASBT, also known as SLC10A2). It has been shown in animal models that plasma cholesterol levels are considerably lowered by specific inhibitors of ASBT, and ASBT is thus a target for hypercholesterolaemia drugs. Here we report the crystal structure of a bacterial homologue of ASBT from Neisseria meningitidis (ASBT(NM)) at 2.2 A. ASBT(NM) contains two inverted structural repeats of five transmembrane helices. A core domain of six helices harbours two sodium ions, and the remaining four helices pack in a row to form a flat, 'panel'-like domain. Overall, the architecture of the protein is remarkably similar to the sodium/proton antiporter NhaA, despite having no detectable sequence homology. The ASBT(NM) structure was captured with the substrate taurocholate present, bound between the core and panel domains in a large, inward-facing, hydrophobic cavity. Residues near this cavity have been shown to affect the binding of specific inhibitors of human ASBT. The position of the taurocholate molecule, together with the molecular architecture, suggests the rudiments of a possible transport mechanism. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT.,Hu NJ, Iwata S, Cameron AD, Drew D Nature. 2011 Oct 5;478(7369):408-11. doi: 10.1038/nature10450. PMID:21976025[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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