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.


5kls

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:40, 6 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
==Structure of CavAb in complex with Br-dihydropyridine derivative UK-59811==
==Structure of CavAb in complex with Br-dihydropyridine derivative UK-59811==
-
<StructureSection load='5kls' size='340' side='right' caption='[[5kls]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+
<StructureSection load='5kls' size='340' side='right'caption='[[5kls]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[5kls]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KLS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KLS FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[5kls]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aliarcobacter_butzleri_RM4018 Aliarcobacter butzleri RM4018]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KLS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KLS FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6UC:O3-ETHYL+O5-METHYL+(4R)-4-(2-BROMOPHENYL)-2-[2-(DIMETHYLAMINO)ETHOXYMETHYL]-6-METHYL-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLATE'>6UC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MC3:1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE'>MC3</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.299&#8491;</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=5kls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kls OCA], [http://pdbe.org/5kls PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kls RCSB], [http://www.ebi.ac.uk/pdbsum/5kls PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kls ProSAT]</span></td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6UC:O3-ETHYL+O5-METHYL+(4R)-4-(2-BROMOPHENYL)-2-[2-(DIMETHYLAMINO)ETHOXYMETHYL]-6-METHYL-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLATE'>6UC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MC3:1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE'>MC3</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=5kls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kls OCA], [https://pdbe.org/5kls PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kls RCSB], [https://www.ebi.ac.uk/pdbsum/5kls PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kls ProSAT]</span></td></tr>
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[https://www.uniprot.org/uniprot/A8EVM5_ALIB4 A8EVM5_ALIB4]
-
Ca2+ antagonist drugs are widely used in therapy of cardiovascular disorders. Three chemical classes of drugs bind to three separate, but allosterically interacting, receptor sites on CaV1.2 channels, the most prominent voltage-gated Ca2+ (CaV) channel type in myocytes in cardiac and vascular smooth muscle. The 1,4-dihydropyridines are used primarily for treatment of hypertension and angina pectoris and are thought to act as allosteric modulators of voltage-dependent Ca2+ channel activation, whereas phenylalkylamines and benzothiazepines are used primarily for treatment of cardiac arrhythmias and are thought to physically block the pore. The structural basis for the different binding, action, and therapeutic uses of these drugs remains unknown. Here we present crystallographic and functional analyses of drug binding to the bacterial homotetrameric model CaV channel CaVAb, which is inhibited by dihydropyridines and phenylalkylamines with nanomolar affinity in a state-dependent manner. The binding site for amlodipine and other dihydropyridines is located on the external, lipid-facing surface of the pore module, positioned at the interface of two subunits. Dihydropyridine binding allosterically induces an asymmetric conformation of the selectivity filter, in which partially dehydrated Ca2+ interacts directly with one subunit and blocks the pore. In contrast, the phenylalkylamine Br-verapamil binds in the central cavity of the pore on the intracellular side of the selectivity filter, physically blocking the ion-conducting pathway. Structure-based mutations of key amino-acid residues confirm drug binding at both sites. Our results define the structural basis for binding of dihydropyridines and phenylalkylamines at their distinct receptor sites on CaV channels and offer key insights into their fundamental mechanisms of action and differential therapeutic uses in cardiovascular diseases.
+
-
 
+
-
Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs.,Tang L, El-Din TM, Swanson TM, Pryde DC, Scheuer T, Zheng N, Catterall WA Nature. 2016 Aug 24;537(7618):117-121. doi: 10.1038/nature19102. PMID:27556947<ref>PMID:27556947</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 5kls" style="background-color:#fffaf0;"></div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Catterall, W A]]
+
[[Category: Aliarcobacter butzleri RM4018]]
-
[[Category: EL-Din, T M.Gamal]]
+
[[Category: Large Structures]]
-
[[Category: Pryde, D C]]
+
[[Category: Catterall WA]]
-
[[Category: Scheuer, T]]
+
[[Category: Gamal EL-Din TM]]
-
[[Category: Swanson, T M]]
+
[[Category: Pryde DC]]
-
[[Category: Tang, L]]
+
[[Category: Scheuer T]]
-
[[Category: Zheng, N]]
+
[[Category: Swanson TM]]
-
[[Category: Transport protein]]
+
[[Category: Tang L]]
-
[[Category: Voltage-gated calcium channel]]
+
[[Category: Zheng N]]

Current revision

Structure of CavAb in complex with Br-dihydropyridine derivative UK-59811

PDB ID 5kls

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5kls"
Personal tools