Table 2.
Overview of available crystal structures of the ligand-bound GR LBD, retrieved from the Protein Data Bank (PDB).
| PDB ID | Ligand | GR Region + Mutations | Species | Cofactor Peptide | GRE Sequence | Method | Ref. |
|---|---|---|---|---|---|---|---|
| 1M2Z | Dex | 521–777 F602S |
H. sapiens | PVSPKKKENALLRYLLDKDDT (NCOA2) | / | XRD | [142] |
| 1NHZ | RU-486 | 500–777 N517D, F602S, C638D |
H. sapiens | / | / | XRD | [147] |
| 1P93 | Dex | 500–777 N517D, F602S, C638D |
H. sapiens | KENALLRYLLDK (NCOA2) |
/ | XRD | [147] |
| 3BQD | Deacyl-cortivazol (DAC) | 525–777 F602S |
H. sapiens | AQQKSLLQQLLTE (NCOA1) |
/ | XRD | [145] |
| 3CLD | Fluticasone furoate (GW6) | 521–777 F602Y, C638G |
H. sapiens | KENALLRYLLDK (NCOA2) |
/ | XRD | [148] |
| 3E7C | GSK866 | 521–777 F602Y, C638G |
H. sapiens | ENALLRYLLDK (NCOA2) |
/ | XRD | [149] |
| 3GN8 | Dex | 529–777 N.A. |
Ancestral | PVSPKKKENARYLLDKDDT (NCOA2) |
/ | XRD | [150] |
| 3H52 | RU-486 | 528–777 F602S, C638D, E684A, E688A, W712S |
H. sapiens | ASNLGLEDIIRKALMGSFD (NCOR1) |
/ | XRD | [151] |
| 3K22 | alaninamide 10 | 521–777 F602Y, C638G |
H. sapiens | KENALLRYLLDK (NCOA2) |
/ | XRD | [152] |
| 3K23 | D-prolinamide 11 | 521–777 F602Y, C638G |
H. sapiens | KENALLRYLLDK (NCOA2) |
/ | XRD | [152] |
| 3MNE | Dex | 527–783 F617S |
M. musculus | KENALLRYLLDKD (NCOA2) |
/ | XRD | [153] |
| 3MNO | Dex | 527–783 F608S, A611V |
M. musculus | KENALLRYLLDKD (NCOA2) |
/ | XRD | [153] |
| 3MNP | Dex | 527–783 A611V, V708A, E711G |
M. musculus | KENALLRYLLDKD (NCOA2) |
/ | XRD | [153] |
| 4CSJ | Compound 30 (NN7) | 500–777 N517D, V571M, F602S, C638D |
H. sapiens | ENALLRYLLDKDD (NCOA2) |
/ | XRD | [154] |
| 4E2J | mometasone furoate | Synthetic 250AA fragment, ancestral GR | Ancestral | NCOA2 (741–752) | / | [155] | |
| 4LSJ | Compound 10 (LSJ) | 522–777 F602Y, C638G |
H. sapiens | HSSRLWELLMEAT (Synthetic D30 peptide) |
/ | XRD | [156] |
| 4MDD | Compound 8 Non-steroidal antagonist |
522–777 L525S, L528S, L535A, V538T, F602Y, C638D, E684A, E688A, W712S |
H. sapiens | NLGLEDIIRKALMGS (NCOR1) |
/ | XRD | [157] |
| 4P6W | Mometasone Furoate | 526–777 F602A, C622Y, T668V, S674T, V675I, K699A, K703A |
H. sapiens | ANALLRYLLDKD (NCOA2) |
/ | XRD | [158] |
| 4P6X | Cortisol | 523–777 F602A, C622Y, T668V, S674T, V675I, E684A, E688A |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [158] |
| 4UDC | Dex | 500–777 N517D, F602S, C638D |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [159] |
| 4UDD | Desisobutyryl-ciclesonide | 500–777 N517D, V571M, F602S, C638D |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [159] |
| 5G3J | Compound 15 (E7T) | 500–777 N517D, V571M, F602S, C638D |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [160] |
| 5G5W | Compound 8b (R8C) | 500–777 N517D, V571M, F602S, C638D |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [161] |
| 5NFP | Budesonide | 500–777 N517D, V571M, F602S, C638D, |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [162] |
| 5NFT | AZD5423 | 500–777 N517D, V571M, F602S, C638D, E638A, W712S |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [162] |
| 5UC1 | RU-486 | 519–727 (GRβ) F599S |
H. glaber | / | / | XRD | [163] |
| 5UC3 | RU-486 | 522–777 L733K, N734P |
H. sapiens | / | / | XRD | / |
| 6DXK | Compound 11 | 522–777 L525S, L528S, L535A, V538T, F602Y, C638D, E684A, E688A? W712S |
H. sapiens | / | / | XRD | [164] |
| 6EL6 | Compound 4 | 500–777 N517D, V571M, F602S, C638D |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [165] |
| 6EL7 | Compound 31 | 500–777 N517D, V571M, F602S, C638D, E684A, W712S |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [165] |
| 6EL9 | AZD9567 | 500–777 N517D, V571M, F602S, C638D, E684A, W712S |
H. sapiens | KENALLRYLLDKDD (NCOA2) |
/ | XRD | [165] |
| 6NWK | Dex | 529–777 N.A. |
Ancestral | PSLLKKLLLAPA (PGC1α) |
/ | XRD | [166] |
| 6NWL | Cortisol | 529–777 N.A. |
Ancestral | PSLLKKLLLAPA (PGC1α) |
/ | XRD | [166] |
| 7KRJ | Dex | 520–777 F602S |
H. sapiens | Hsp90, p23 (full-length) | / | CEM | [167] |
| 7KW7 | / | Full-length (LBD structure) |
H. sapiens | Hsp90, Hsp70, Hop (full-length) | / | CEM | [168] |
| 7PRV | Fluticasone furoate (GW6) | 385–777 S404A N517D V571M F602S C638D |
H. sapiens | PPQEAEEPSLLKKLLLAPANT (PGC1α) |
TACAGAACATTTTGTCCGTCGAC (Sgk1 23 bp; overhang) |
XRD | [122] |
| 7PRW | Velsecorat | 385–777 S404A N517D V571M F602S C638D |
H. sapiens | PPQEAEEPSLLKKLLLAPANT (PGC1α) |
GTACAGAACATTTTGTCCGTCGA (Sgk1 23 bp; blunt) |
XRD | [122] |
| 7PRX | Velsecorat | 529–777 | H. sapiens | PPQEAEEPSLLKKLLLAPANT (PGC1α) |
/ | XRD | [122] |
Dex, dexamethasone; NCOA2, nuclear receptor coactivator 2; XRD, X-ray diffraction; NCOA1, nuclear receptor coactivator 1; NCOR1, nuclear receptor corepressor 1; PGC1α, Peroxisome proliferator-activated receptor gamma coactivator 1 alpha; Hsp90, heat shock protein; CEM, cryo-electron microscopy; LBD, ligand-binding domain; Hsp70, heat shock protein 70, Hop, Hsp90-Hsp70 organizing protein.