2AWH

Human Nuclear Receptor-Ligand Complex 1

Summary for 2AWH

• Entry DOI: 10.2210/pdb2awh/pdb
• Descriptor: Peroxisome proliferator activated receptor delta, heptyl beta-D-glucopyranoside, VACCENIC ACID, ... (4 entities in total)
• Functional Keywords: nuclear receptor, protein-ligand complex, ppar, gene regulation
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 62488.96

Authors

Fyffe, S.A.,Alphey, M.S.,Buetow, L.,Smith, T.K.,Ferguson, M.A.J.,Sorensen, M.D.,Bjorkling, F.,Hunter, W.N. (deposition date: 2005-09-01, release date: 2006-02-14, Last modification date: 2024-03-13)

Primary citation

Fyffe, S.A.,Alphey, M.S.,Buetow, L.,Smith, T.K.,Ferguson, M.A.J.,Sorensen, M.D.,Bjorkling, F.,Hunter, W.N.
Recombinant Human PPAR-beta/delta Ligand-binding Domain is Locked in an Activated Conformation by Endogenous Fatty Acids
J.Mol.Biol., 356:1005-1013, 2006

PubMed Abstract: High-resolution crystallographic structures of recombinant human peroxisome proliferator-activated receptor ligand-binding domain (isotype beta/delta) reveal a fatty acid in the binding site. Mass spectrometry confirmed the presence of C16:0, C16:1, C18:0 and C18:1 in a ratio of approximately 3:2:1:4 with 11, Z-octadecenoic acid (cis-vaccenic acid) identified as the predominant species. These are endogenous fatty acids acquired from the bacterial expression system, and serve to lock the ligand-binding domain into the activated conformation. A requirement for crystal growth, the additive n-heptyl-beta-d-glucopyranoside, binds near the activation function helix where recognition of co-activator proteins occurs. Our observations suggest potential physiological ligands for human PPAR-beta/delta and highlight that reported binding studies must be treated with caution unless endogenous fatty acids have been removed from the sample prior to analysis.

PubMed: 16405912
DOI: 10.1016/j.jmb.2005.12.047

Experimental method

X-RAY DIFFRACTION (2 Å)