PDBsum entry 2jk5

Immune system/metal transport

PDB id: 2jk5

Contents

Protein chains

219 a.a. *

212 a.a. *

103 a.a. *

Ligands

F09

L2C

TBA

HP6

Metals

_CO

__K ×6

Waters ×204

* Residue conservation analysis

PDB id:

2jk5

Name:

Immune system/metal transport

Title:

Potassium channel kcsa in complex with tetrabutylammonium in high k

Structure:

Antibody fab fragment light chain. Chain: a. Engineered: yes. Antibody fab fragment heavy chain. Chain: b. Engineered: yes. Voltage-gated potassium channel. Chain: c. Fragment: residues 1-124.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: mus musculus. Expression_system_taxid: 10090. Other_details: hybridoma. Streptomyces lividans. Organism_taxid: 1916. Expressed in: escherichia coli.

Resolution:

2.40Å R-factor: 0.205 R-free: 0.249

Authors:

M.J.Lenaeus,P.J.Focia,T.Wagner,A.Gross

Key ref:

M.J.Lenaeus et al. (2014). Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site. Biochemistry, 53, 5365-5373. PubMed id: 25093676 DOI: 10.1021/bi500525s

Date:

15-Aug-08 Release date: 17-Nov-09

Protein chain

No UniProt id for this chain

Struc: 219 a.a.

Protein chain

No UniProt id for this chain

Struc: 212 a.a.

Protein chain

P0A334  (KCSA_STRLI) -  pH-gated potassium channel KcsA from Streptomyces lividans

Seq: 160 a.a.

Struc: 103 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1021/bi500525s

Biochemistry 53:5365-5373 (2014)

PubMed id: 25093676

Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site.

M.J.Lenaeus, D.Burdette, T.Wagner, P.J.Focia, A.Gross.

ABSTRACT

Potassium channels allow for the passive movement of potassium ions across the cell membrane and are instrumental in controlling the membrane potential in all cell types. Quaternary ammonium (QA) compounds block potassium channels and have long been used to study the functional and structural properties of these channels. Here we describe the interaction between three symmetrical hydrophobic QAs and the prokaryotic potassium channel KcsA. The structures demonstrate the presence of a hydrophobic pocket between the inner helices of KcsA and provide insight into the binding site and blocking mechanism of hydrophobic QAs. The structures also reveal a structurally hidden pathway between the central cavity and the outside membrane environment reminiscent of the lateral fenestration observed in sodium channels that can be accessed through small conformational changes in the pore wall. We propose that the hydrophobic binding pocket stabilizes the alkyl chains of long-chain QA molecules and may play a key role in hydrophobic drug binding in general.