2ZVT

Cys285Ser mutant PPARgamma ligand-binding domain complexed with 15-deoxy-delta12,14-prostaglandin J2

Summary for 2ZVT

• Entry DOI: 10.2210/pdb2zvt/pdb
• Related: 2ZK1
• Descriptor: Peroxisome proliferator-activated receptor gamma, (5E,14E)-11-oxoprosta-5,9,12,14-tetraen-1-oic acid (3 entities in total)
• Functional Keywords: anti parallel helix sandwich, activator, alternative splicing, diabetes mellitus, disease mutation, dna-binding, metal-binding, nucleus, obesity, phosphoprotein, polymorphism, receptor, transcription, transcription regulation, zinc, zinc-finger
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 65662.04

Authors

Waku, T.,Oyama, T.,Shiraki, T.,Morikawa, K. (deposition date: 2008-11-19, release date: 2009-10-06, Last modification date: 2023-11-01)

Primary citation

Waku, T.,Shiraki, T.,Oyama, T.,Morikawa, K.
Atomic structure of mutant PPARgamma LBD complexed with 15d-PGJ2: novel modulation mechanism of PPARgamma/RXRalpha function by covalently bound ligands
Febs Lett., 583:320-324, 2009

PubMed Abstract: 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) activates a nuclear receptor heterodimer, peroxisome proliferators-activated receptor gamma (PPARgamma)/ retinoid X receptor (RXRalpha) through covalent binding to Cys285 in PPARgamma ligand-binding domain (LBD). Here, we present the 1.9A crystal structure of C285S mutant LBD complexed with 15d-PGJ(2), corresponding to the non-covalently bound state. The ligand lies adjacent to a hydrogen-bond network around the helix H2 and the nearby beta-sheet. Comparisons with previous structures clarified the relationships between PPARgamma function and conformational alterations of LBD during the process of covalently binding ligands, such as 15d-PGJ(2), and thus suggested a mechanism, by which these ligands modulate PPARgamma/RXRalpha function through conformational changes of the loop following helix H2' and the beta-sheet.

PubMed: 19101554
DOI: 10.1016/j.febslet.2008.12.017

Experimental method

X-RAY DIFFRACTION (1.9 Å)