8AQN: Peroxisome proliferator-activated receptor gamma

Crystal structure of PPARG and NCOR2 with BAY-4931, an inverse agonist (compound 6c). Determined by X-ray diffraction at 1.9 Å resolution. Released 9 Nov 2022.

Method: X-ray diffraction
Resolution: 1.9 Å
Organism: Homo sapiens
Chains: 4
Atoms: 4,946
Mol. weight: 70.07 kDa
Ligands: CA, O0U
Released: 9 Nov 2022

Explore 8AQN in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8AQN contains 39 α-helices and 10 β-strands across 4 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 18 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	206-225	20
α-helix	230-237	8
α-helix	246	1
β-strand	247-249	3	1
α-helix	252-255	4
α-helix	262-264	3
α-helix	267-271	5
β-strand	272-273	2	2
α-helix	274-288	15
α-helix	290-302	13
α-helix	306-308	3
α-helix	311-332	22
β-strand	334-335	2	1
β-strand	338-341	4	1
β-strand	346-349	4	1
α-helix	350-354	5
α-helix	357	1
α-helix	360-362	3
α-helix	365-376	12
α-helix	381-392	12
α-helix	403-424	22
α-helix	431-457	27
β-strand	462-463	2	2
α-helix	467-473	7

Chain B: 18 helices, 4 β-strands

Element	Residues	Length	Sheet
α-helix	211-225	15
α-helix	230-238	9
β-strand	247-249	3	3
α-helix	252-258	7
α-helix	259-261	3
α-helix	280-282	3
α-helix	283-301	19
α-helix	306-308	3
α-helix	311-332	22
β-strand	334-335	2	3
β-strand	338-341	4	3
α-helix	342-344	3
β-strand	346-349	4	3
α-helix	350-354	5
α-helix	357	1
α-helix	360-362	3
α-helix	365-375	11
α-helix	381-392	12
α-helix	403-424	22
α-helix	431-457	27
α-helix	463-465	3
α-helix	466-473	8

Chain C: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2348-2359	12
α-helix	2362-2364	3

Chain D: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2350-2359	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Peroxisome proliferator-activated receptor gamma	A, B	protein	279	Homo sapiens	P37231 (AlphaFold model)
Nuclear receptor corepressor 2	C, D	protein	23	Homo sapiens	Q9Y618 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8AQN_1 Peroxisome proliferator-activated receptor gamma (chains A, B)
GSHMQLNPESADLRALAKHLYDSYIKSFPLTKAKARAILTGKTTDKSPFVIYDMNSLMMG
EDKIKFKHITPLQEQSKEVAIRIFQGCQFRSVEAVQEITEYAKSIPGFVNLDLNDQVTLL
KYGVHEIIYTMLASLMNKDGVLISEGQGFMTREFLKSLRKPFGDFMEPKFEFAVKFNALE
LDDSDLAIFIAVIILSGDRPGLLNVKPIEDIQDNLLQALELQLKLNHPESSQLFAKLLQK
MTDLRQIVTEHVQLLQVIKKTETDMSLHPLLQEIYKDLY

Sequence of entity 2 (C, D), FASTA

>8AQN_2 Nuclear receptor corepressor 2 (chains C, D)
HASTNMGLEAIIRKALMGKYDQW

Ligands and cofactors

ID	Name	Formula	Copies
CA	Calcium ion	Ca	1
O0U	2-chloranyl-~{N}-[2-(4-ethylphenyl)-1,3-benzoxazol-5-yl]-5-nitro-benzamide	C22 H16 Cl N3 O4	2

Water and common crystallization additives (GOL) are not listed.

Primary citation

Discovery and Structure-Based Design of Potent Covalent PPAR gamma Inverse-Agonists BAY-4931 and BAY-0069 . Orsi, D.L., Pook, E., Brauer, N. et al. J Med Chem (2022) 65:14843-14863. DOI 10.1021/acs.jmedchem.2c01379 · PubMed

Other PDB entries of the same protein (UniProt P37231 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9F7W 1.25 Å, Human PPARgamma ligand binding domain in complex with co-activator 1alpha peptide and…
8BF1 1.36 Å, High-resolution structure of unliganded PPAR gamma in complex with the peptide PGC-1 alpha
9V8G 1.39 Å, PPARgamma ligand-binding domain in complex with PG08-NL
9V8H 1.39 Å, PPARgamma ligand-binding domain in complex with PG08-NL and rosiglitazone
8FKC 1.42 Å, Crystal structure of PPARgamma ligand-binding domain in complex with N-CoR peptide and…
6MS7 1.43 Å, Peroxisome proliferator-activated receptor gamma ligand binding domain in complex with a…
9V8D 1.44 Å, PPARgamma ligand-binding domain in complex with PG08
3U9Q 1.52 Å, Ligand binding domain of PPARgamma complexed with Decanoic Acid and PGC-1a peptide
8B94 1.55 Å, Crystal structure of PPARG and NCOR2 with BAY-5516, an inverse agonist
8DKV 1.59 Å, PPARg bound to JTP-426467 and Co-R peptide
3B1M 1.6 Å, Crystal structure of the PPARgamma-LBD complexed with a cercosporamide derivative…
3V9V 1.6 Å, Crystal structure of the PPARgamma-LBD complexed with a cercosporamide derivative…

Browse structure collections

About this viewer

MolViewer shows 8AQN directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.