This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6baa

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Cryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide

6baa, resolution 3.63Å

Structural highlights

6baa is a 8 chain structure with sequence from Black-bellied hamster and Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Kcnj11 (Buffalo rat), ABCC8, SUR (Black-bellied hamster)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KCJ11_RAT] This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity). [ABCC8_CRICR] Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive potassium channels and insulin release.[UniProtKB:Q09428]

Publication Abstract from PubMed

Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic KATP channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63 A resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites. Importantly, the structure shows for the first time that glibenclamide is lodged in the transmembrane bundle of the SUR1-ABC core connected to the first nucleotide binding domain near the inner leaflet of the lipid bilayer. Mutation of residues predicted to interact with glibenclamide in our model led to reduced sensitivity to glibenclamide. Our structure provides novel mechanistic insights of how sulfonylureas and ATP interact with the KATP channel complex to inhibit channel activity.

Anti-diabetic drug binding site in a mammalian KATP channel revealed by Cryo-EM.,Martin GM, Kandasamy B, DiMaio F, Yoshioka C, Shyng SL Elife. 2017 Oct 24;6. pii: e31054. doi: 10.7554/eLife.31054. PMID:29035201^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martin GM, Kandasamy B, DiMaio F, Yoshioka C, Shyng SL. Anti-diabetic drug binding site in a mammalian KATP channel revealed by Cryo-EM. Elife. 2017 Oct 24;6. pii: e31054. doi: 10.7554/eLife.31054. PMID:29035201 doi:http://dx.doi.org/10.7554/eLife.31054

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6baa"

@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide==
-<StructureSection load='6baa' size='340' side='right' caption='[[6baa]], [[Resolution|resolution]] 3.63&Aring;' scene=''>
+<SX load='6baa' size='340' side='right' viewer='molstar' caption='[[6baa]], [[Resolution|resolution]] 3.63&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6baa]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BAA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BAA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6baa]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Black-bellied_hamster Black-bellied hamster] and [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BAA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BAA FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GBM:5-CHLORO-N-(2-{4-[(CYCLOHEXYLCARBAMOYL)SULFAMOYL]PHENYL}ETHYL)-2-METHOXYBENZAMIDE'>GBM</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GBM:5-CHLORO-N-(2-{4-[(CYCLOHEXYLCARBAMOYL)SULFAMOYL]PHENYL}ETHYL)-2-METHOXYBENZAMIDE'>GBM</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6baa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6baa OCA], [http://pdbe.org/6baa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6baa RCSB], [http://www.ebi.ac.uk/pdbsum/6baa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6baa ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kcnj11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), ABCC8, SUR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10034 Black-bellied hamster])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6baa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6baa OCA], [http://pdbe.org/6baa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6baa RCSB], [http://www.ebi.ac.uk/pdbsum/6baa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6baa ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 6baa" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Potassium channel 3D structures|Potassium channel 3D structures]]
 == References ==
 <references/>
 __TOC__
-</StructureSection>
+</SX>
+[[Category: Black-bellied hamster]]
+[[Category: Buffalo rat]]
+[[Category: Large Structures]]
 [[Category: Martin, G M]]
 [[Category: Shyng, S L]]

6baa

From Proteopedia

Current revision

Cryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox