8B8W: PPARG and NCOR2 with an inverse agonist

Crystal structure of PPARG and NCOR2 with an inverse agonist (compound 7a). Determined by X-ray diffraction at 1.86 Å resolution. Released 28 Dec 2022.

Method: X-ray diffraction
Resolution: 1.86 Å
Organism: Homo sapiens
Chains: 4
Atoms: 4,641
Mol. weight: 69.82 kDa
Ligands: Q2X
Released: 28 Dec 2022

Explore 8B8W in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8B8W contains 30 α-helices and 8 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: 14 helices, 4 β-strands

Element	Residues	Length	Sheet
α-helix	206-225	20
α-helix	230-237	8
α-helix	244-246	3
β-strand	247-249	3	1
α-helix	252-258	7
α-helix	277-302	26
α-helix	311-330	20
α-helix	331-333	3
β-strand	334-335	2	1
β-strand	338-341	4	1
β-strand	346-349	4	1
α-helix	350-355	6
α-helix	360-362	3
α-helix	365-375	11
α-helix	381-392	12
α-helix	403-424	22
α-helix	431-459	29
α-helix	467-472	6

Chain B: 14 helices, 4 β-strands

Element	Residues	Length	Sheet
α-helix	206-225	20
α-helix	230-237	8
α-helix	244-246	3
β-strand	247-249	3	2
α-helix	252-259	8
α-helix	277-301	25
α-helix	306-308	3
α-helix	311-331	21
β-strand	334-335	2	2
β-strand	338-341	4	2
β-strand	346-349	4	2
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	431-459	29

Chain C: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2349-2358	10

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

>8B8W_1 Peroxisome proliferator-activated receptor gamma (chains A, B)
GSHMQLNPESADLRALAKHLYDSYIKSFPLTKAKARAILTGKTTDKSPFVIYDMNSLMMG
EDKIKFKHITPLQEQSKEVAIRIFQGCQFRSVEAVQEITEYAKSIPGFVNLDLNDQVTLL
KYGVHEIIYTMLASLMNKDGVLISEGQGFMTREFLKSLRKPFGDFMEPKFEFAVKFNALE
LDDSDLAIFIAVIILSGDRPGLLNVKPIEDIQDNLLQALELQLKLNHPESSQLFAKLLQK
MTDLRQIVTEHVQLLQVIKKTETDMSLHPLLQEIYKDLY

Sequence of entity 2 (C, D), FASTA

>8B8W_2 Nuclear receptor corepressor 2 (chains C, D)
HASTNMGLEAIIRKALMGKYDQW

Ligands and cofactors

ID	Name	Formula	Copies
Q2X	4-chloranyl-~{N}3-phenyl-~{N}1-(phenylmethyl)benzene-1,3-dicarboxamide	C21 H17 Cl N2 O2	2

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

Primary citation

Discovery and characterization of orally bioavailable 4-chloro-6-fluoroisophthalamides as covalent PPARG inverse-agonists. Orsi, D.L., Ferrara, S.J., Siegel, S. et al. Bioorg Med Chem (2022) 78:117130-117130. DOI 10.1016/j.bmc.2022.117130 · 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…

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