6JUH

structure of CavAb in complex with efonidipine

PDB DOI: https://doi.org/10.2210/pdb6JUH/pdb

Classification: MEMBRANE PROTEIN
Organism(s): Aliarcobacter butzleri RM4018
Expression System: Trichoplusia ni
Mutation(s): Yes
Membrane Protein: Yes OPMPDBTMMemProtMD

Deposited: 2019-04-13 Released: 2019-11-06
Deposition Author(s): Tang, L., Xu, F.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.00 ?
R-Value Free: 0.291
R-Value Work: 0.235
R-Value Observed: 0.238

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Structural basis for efonidipine block of a voltage-gated Ca2+channel.

Xu, F., Xiong, W., Huang, Y., Shen, J., Zhou, D., Tang, L.

(2019) Biochem Biophys Res Commun 513: 631-634

PubMed: 30981510 Search on PubMed
DOI: https://doi.org/10.1016/j.bbrc.2019.03.176
Primary Citation of Related Structures:
6JUH

PubMed Abstract:
Efonidipine is a dual L-/T- type calcium channel blocker with a slow onset of action and a long lasting effect that exibihits antihypertensive and nephroprotective effects. differs from most other DHPs which can induce reflex tachycardia. Efonidipine reduces blood pressure without decreasing cardiac output and exerts organ-protective effects on the heart and kidney. In order to investigate how efonidipine block voltage-gated Ca ²⁺ channel, we determined the crystal structure of Ca _VAb in complex with efonidipine at atomic resolution using x-ray crystallography. Our results reveal that efonidipine targets the central cavity of a model voltage-gated calcium channel underneath its selectivity filter and occlude the channel in an inactivated state. Binding of efonidipine does not break down the fourfold symmetry of the quaternary structure and its pore structure. Our work provides the structural basis for efonidipine block of a voltage-gated Ca ²⁺ channel at the molecular level.

Organizational Affiliation

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, 61004, China.

Macromolecule Content

Total Structure Weight: 131.19 kDa
Atom Count: 8,851
Modelled Residue Count: 1,050
Deposited Residue Count: 1,068
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Ion transport protein	A, B, C, D	267	Aliarcobacter butzleri RM4018	Mutation(s): 3 Membrane Entity: Yes
UniProt
Find proteins for A8EVM5 (Aliarcobacter butzleri (strain RM4018)) Explore A8EVM5 Go to UniProtKB: A8EVM5
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	A8EVM5
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
PX4 Query on PX4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain J [auth B] SDF format, chain M [auth C] SDF format, chain N [auth C] MOL2 format, chain F [auth A] MOL2 format, chain J [auth B] MOL2 format, chain M [auth C] MOL2 format, chain N [auth C] mmCIF format, chain F [auth A] mmCIF format, chain J [auth B] mmCIF format, chain M [auth C] mmCIF format, chain N [auth C]	F [auth A], J [auth B], M [auth C], N [auth C]	1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE C₃₆ H₇₃ N O₈ P CITHEXJVPOWHKC-UUWRZZSWSA-O		Interactions Focus chain F [auth A] Focus chain J [auth B] Focus chain M [auth C] Focus chain N [auth C] Interactions & Density Focus chain F [auth A] Focus chain J [auth B] Focus chain M [auth C] Focus chain N [auth C]
MC3 Query on MC3 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain I [auth B] SDF format, chain L [auth C] SDF format, chain R [auth D] MOL2 format, chain E [auth A] MOL2 format, chain I [auth B] MOL2 format, chain L [auth C] MOL2 format, chain R [auth D] mmCIF format, chain E [auth A] mmCIF format, chain I [auth B] mmCIF format, chain L [auth C] mmCIF format, chain R [auth D]	E [auth A], I [auth B], L [auth C], R [auth D]	1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE C₃₆ H₇₂ N O₈ P CITHEXJVPOWHKC-UUWRZZSWSA-N		Interactions Focus chain E [auth A] Focus chain I [auth B] Focus chain L [auth C] Focus chain R [auth D] Interactions & Density Focus chain E [auth A] Focus chain I [auth B] Focus chain L [auth C] Focus chain R [auth D]
C9X Query on C9X Download Ideal Coordinates CCD File SDF format, chain Q [auth D] MOL2 format, chain Q [auth D] mmCIF format, chain Q [auth D]	Q [auth D]	2-[phenyl-(phenylmethyl)amino]ethyl (4~{R})-5-(5,5-dimethyl-2-oxidanylidene-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate C₃₄ H₃₈ N₃ O₇ P NSVFSAJIGAJDMR-WJOKGBTCSA-N		Interactions Focus chain Q [auth D] Interactions & Density Focus chain Q [auth D]
G3P Query on G3P Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain O [auth C] SDF format, chain P [auth C] SDF format, chain S [auth D] MOL2 format, chain G [auth A] MOL2 format, chain O [auth C] MOL2 format, chain P [auth C] MOL2 format, chain S [auth D] mmCIF format, chain G [auth A] mmCIF format, chain O [auth C] mmCIF format, chain P [auth C] mmCIF format, chain S [auth D]	G [auth A], O [auth C], P [auth C], S [auth D]	SN-GLYCEROL-3-PHOSPHATE C₃ H₉ O₆ P AWUCVROLDVIAJX-GSVOUGTGSA-N		Interactions Focus chain G [auth A] Focus chain O [auth C] Focus chain P [auth C] Focus chain S [auth D] Interactions & Density Focus chain G [auth A] Focus chain O [auth C] Focus chain P [auth C] Focus chain S [auth D]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain K [auth C] MOL2 format, chain H [auth B] MOL2 format, chain K [auth C] mmCIF format, chain H [auth B] mmCIF format, chain K [auth C]	H [auth B], K [auth C]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain H [auth B] Focus chain K [auth C] Interactions & Density Focus chain H [auth B] Focus chain K [auth C]