› 5cgc

X-ray diffraction
3.1Å resolution

Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile

Released:
DOI: 10.2210/pdb5cgc/pdb
PDB entry 5cgc coloured by chain, front view.
PDB entry 5cgc coloured by chain, side view.
PDB entry 5cgc coloured by chain, top view.
Source organisms:
Primary publication:
Fragment and Structure-Based Drug Discovery for a Class C GPCR: Discovery of the mGlu5 Negative Allosteric Modulator HTL14242 (3-Chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile).
Christopher JA, Aves SJ, Bennett KA, Doré AS, Errey JC, Jazayeri A, Marshall FH, Okrasa K, Serrano-Vega MJ, Tehan BG, Wiggin GR, Congreve M
J Med Chem 58 6653-64 (2015)
PMID: 26225459

Function and Biology Details

Reaction catalysed: 
Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-132987 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Endolysin; Metabotropic glutamate receptor 5 Chain: A
Molecule details ›
Chain: A
Length: 444 amino acids
Theoretical weight: 49.8 KDa
Source organisms: Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P41594 (Residues: 569-678, 680-836; Coverage: 22%)
  • Canonical: P00720 (Residues: 2-162; Coverage: 98%)
Gene names: E, GPRC1E, GRM5, MGLUR5
Sequence domains:

Ligands and Environments

3 bound ligands:
Ligand OLA 4 x OLA
Ligand MES 1 x MES
Ligand 51D 1 x 51D
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I24
Spacegroup: C2
Unit cell:
a: 143.021Å b: 43.818Å c: 81.617Å
α: 90° β: 99.2° γ: 90°
R-values:
R R work R free
0.236 0.234 0.287
Expression system: Spodoptera frugiperda

Quick links

Citations

28 review citations

How Ligands Illuminate GPCR Molecular Pharmacology.
Wacker et al. (2017)
27 more

23 mentions without citation

G protein-coupled receptors: structure- and function-based drug discovery.
Yang et al. (2021)
22 more