PDBsum entry 6hpp

Membrane protein

PDB id: 6hpp

Contents

Protein chains

311 a.a.

Ligands

LMT ×6

PPI ×10

Metals

_CL ×7

_NA ×6

Waters ×22

PDB id:

6hpp

Name:

Membrane protein

Title:

X-ray structure of glic in complex with propionate

Structure:

Proton-gated ion channel. Chain: a, b, c, d, e. Synonym: glic,ligand-gated ion channel,lgic. Engineered: yes

Source:

Gloeobacter violaceus (strain pcc 7421). Organism_taxid: 251221. Strain: pcc 7421. Gene: glvi, glr4197. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

3.20Å R-factor: 0.195 R-free: 0.201

Authors:

Z.Fourati,M.Delarue

Key ref:

Z.Fourati et al. (2020). Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel. Acta Crystallogr D Struct Biol, 76, 668-675. PubMed id: 32627739 DOI: 10.1107/S205979832000772X

Date:

21-Sep-18 Release date: 09-Oct-19

Protein chains

Q7NDN8  (GLIC_GLOVI) -  Proton-gated ion channel from Gloeobacter violaceus (strain ATCC 29082 / PCC 7421)

Seq: 359 a.a.

Struc: 311 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1107/S205979832000772X

Acta Crystallogr D Struct Biol 76:668-675 (2020)

PubMed id: 32627739

Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel.

Z.Fourati, L.Sauguet, M.Delarue.

ABSTRACT

GLIC is a bacterial homologue of the pentameric ligand-gated ion channels (pLGICs) that mediate the fast chemical neurotransmission of nerve signalling in eukaryotes. Because the activation and allosteric modulation features are conserved among prokaryotic and eukaryotic pLGICs, GLIC is commonly used as a model to study the allosteric transition and structural pharmacology of pLGICs. It has previously been shown that GLIC is inhibited by some carboxylic acid derivatives. Here, experimental evidence for carboxylate binding to GLIC is provided by solving its X-ray structures with a series of monocarboxylate and dicarboxylate derivatives, and two carboxylate-binding sites are described: (i) the `intersubunit' site that partially overlaps the canonical pLGIC orthosteric site and (ii) the `intrasubunit' vestibular site, which is only occupied by a subset of the described derivatives. While the intersubunit site is widely conserved in all pLGICs, the intrasubunit site is only conserved in cationic eukaryotic pLGICs. This study sheds light on the importance of these two extracellular modulation sites as potential drug targets in pLGICs.