PDBsum entry 6dgo

Transcription/transcription inhibitor

PDB id: 6dgo

Contents

Protein chains

260 a.a.

Ligands

GD4

PDB id:

6dgo

Name:

Transcription/transcription inhibitor

Title:

Crystal structure of human ppargamma ligand binding domain in complex with troglitazone

Structure:

Peroxisome proliferator-activated receptor gamma. Chain: a, b. Synonym: ppar-gamma,nuclear receptor subfamily 1 group c member 3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pparg, nr1c3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

3.10Å R-factor: 0.202 R-free: 0.276

Authors:

J.Shang,D.J.Kojetin

Key ref:

J.Shang et al. (2019). Quantitative structural assessment of graded receptor agonism. Proc Natl Acad Sci U S A, 116, 22179-22188. PubMed id: 31611383 DOI: 10.1073/pnas.1909016116

Date:

17-May-18 Release date: 22-May-19

Protein chains

P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma from Homo sapiens

Seq: 505 a.a.

Struc: 260 a.a.

DOI no: 10.1073/pnas.1909016116

Proc Natl Acad Sci U S A 116:22179-22188 (2019)

PubMed id: 31611383

Quantitative structural assessment of graded receptor agonism.

J.Shang, R.Brust, P.R.Griffin, T.M.Kamenecka, D.J.Kojetin.

ABSTRACT

Ligand-receptor interactions, which are ubiquitous in physiology, are described by theoretical models of receptor pharmacology. Structural evidence for graded efficacy receptor conformations predicted by receptor theory has been limited but is critical to fully validate theoretical models. We applied quantitative structure-function approaches to characterize the effects of structurally similar and structurally diverse agonists on the conformational ensemble of nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). For all ligands, agonist functional efficacy is correlated to a shift in the conformational ensemble equilibrium from a ground state toward an active state, which is detected by NMR spectroscopy but not observed in crystal structures. For the structurally similar ligands, ligand potency and affinity are also correlated to efficacy and conformation, indicating ligand residence times among related analogs may influence receptor conformation and function. Our results derived from quantitative graded activity-conformation correlations provide experimental evidence and a platform with which to extend and test theoretical models of receptor pharmacology to more accurately describe and predict ligand-dependent receptor activity.