1K74

The 2.3 Angstrom resolution crystal structure of the heterodimer of the human PPARgamma and RXRalpha ligand binding domains respectively bound with GW409544 and 9-cis retinoic acid and co-activator peptides.

Summary for 1K74

• Entry DOI: 10.2210/pdb1k74/pdb
• Related: 1K7L 1fm6 1fm9
• Descriptor: Retinoic acid receptor RXR-alpha, Peroxisome proliferator activated receptor gamma, steroid receptor coactivator, ... (6 entities in total)
• Functional Keywords: the heterodimer of the nuclear receptor ligand binding domains of rxralpha and ppargamma bound respectively with 9-cis retinoic acid and gw409544 and coactivator peptides, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P19793 P37231
• Total number of polymer chains: 4
• Total formula weight: 65517.86

Authors

Xu, H.E.,Lambert, M.H.,Montana, V.G.,Moore, L.B.,Collins, J.L.,Oplinger, J.A.,Kliewer, S.A.,Gampe Jr., R.T.,McKee, D.D.,Moore, J.T.,Willson, T.M. (deposition date: 2001-10-18, release date: 2001-12-05, Last modification date: 2024-02-07)

Primary citation

Xu, H.E.,Lambert, M.H.,Montana, V.G.,Plunket, K.D.,Moore, L.B.,Collins, J.L.,Oplinger, J.A.,Kliewer, S.A.,Gampe Jr., R.T.,McKee, D.D.,Moore, J.T.,Willson, T.M.
Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors.
Proc.Natl.Acad.Sci.USA, 98:13919-13924, 2001

PubMed Abstract: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of glucose, lipid, and cholesterol metabolism. We report the x-ray crystal structure of the ligand binding domain of PPAR alpha (NR1C1) as a complex with the agonist ligand GW409544 and a coactivator motif from the steroid receptor coactivator 1. Through comparison of the crystal structures of the ligand binding domains of the three human PPARs, we have identified molecular determinants of subtype selectivity. A single amino acid, which is tyrosine in PPAR alpha and histidine in PPAR gamma, imparts subtype selectivity for both thiazolidinedione and nonthiazolidinedione ligands. The availability of high-resolution cocrystal structures of the three PPAR subtypes will aid the design of drugs for the treatments of metabolic and cardiovascular diseases.

PubMed: 11698662
DOI: 10.1073/pnas.241410198

Experimental method

X-RAY DIFFRACTION (2.3 Å)