Fluorine in PDB 8b91: Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1)

The structure of Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1), PDB code: 8b91 was solved by A.Friberg, D.L.Orsi, E.Pook, S.Siegel, C.T.Lemke, T.Stellfeld, V.Puetter, J.Goldstein, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	49.47 / 2.23
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	60.355, 86.134, 120.855, 90, 90, 90
R / Rfree (%)	20.2 / 22.8

The structure of Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1) also contains other interesting chemical elements:

Chlorine

(Cl)

1 atom

The binding sites of Fluorine atom in the Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1) (pdb code 8b91). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1), PDB code: 8b91:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1) within 5.0Å range: probe atom residue distance (Å) B Occ A:F501 b:60.6 occ:1.00 F7 A:Q4O501 0.0 60.6 1.0 C6 A:Q4O501 1.3 54.3 1.0 C5 A:Q4O501 2.3 54.9 1.0 C1 A:Q4O501 2.4 53.0 1.0 C23 A:Q4O501 2.9 50.9 1.0 N24 A:Q4O501 2.9 48.0 1.0 CE A:MET348 3.1 37.5 1.0 CG2 A:ILE281 3.3 38.2 1.0 C4 A:Q4O501 3.6 58.1 1.0 SD A:MET348 3.6 40.0 1.0 C2 A:Q4O501 3.6 54.8 1.0 C28 A:Q4O501 3.8 50.0 1.0 O25 A:Q4O501 3.9 50.3 1.0 O A:ILE281 4.1 38.6 1.0 C3 A:Q4O501 4.1 56.3 1.0 C26 A:Q4O501 4.2 50.4 1.0 CG2 A:ILE341 4.3 36.5 1.0 C27 A:Q4O501 4.4 52.8 1.0 CB A:ILE281 4.4 37.5 1.0 CD2 A:LEU353 4.6 29.5 1.0 CA A:ILE281 4.6 40.3 1.0 C A:ILE281 4.6 38.5 1.0 C29 A:Q4O501 4.6 57.1 1.0 CD1 A:ILE341 4.7 36.2 1.0 CG1 A:ILE281 4.9 36.7 1.0 CL8 A:Q4O501 5.0 65.4 1.0

Fluorine binding site 2 out of 4 in the Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1) within 5.0Å range: probe atom residue distance (Å) B Occ A:F501 b:53.0 occ:1.00 F18 A:Q4O501 0.0 53.0 1.0 C16 A:Q4O501 1.4 49.8 1.0 C15 A:Q4O501 2.3 51.5 1.0 C17 A:Q4O501 2.4 47.8 1.0 O19 A:Q4O501 2.6 60.2 1.0 C20 A:Q4O501 3.1 63.4 1.0 CB A:ALA292 3.2 41.4 1.0 CG2 A:ILE326 3.6 29.6 1.0 C14 A:Q4O501 3.6 46.3 1.0 C12 A:Q4O501 3.7 53.9 1.0 CG1 A:ILE326 3.9 30.9 1.0 O A:ARG288 3.9 36.6 1.0 CA A:SER289 4.0 37.5 1.0 F22 A:Q4O501 4.1 68.5 1.0 F21 A:Q4O501 4.1 63.2 1.0 C13 A:Q4O501 4.1 51.0 1.0 C A:ARG288 4.2 37.2 1.0 N A:SER289 4.2 38.0 1.0 CB A:ILE326 4.3 29.0 1.0 OG A:SER289 4.3 41.8 1.0 CD1 A:ILE326 4.3 30.9 1.0 NH2 A:ARG288 4.3 43.2 1.0 CG A:ARG288 4.6 44.4 1.0 CA A:ALA292 4.6 42.9 1.0 CB A:SER289 4.8 37.8 1.0 O10 A:Q4O501 4.8 55.0 1.0 CA A:ILE326 4.8 27.1 1.0 N11 A:Q4O501 4.9 55.8 1.0 O A:SER289 4.9 31.2 1.0 C A:SER289 5.0 36.2 1.0

Fluorine binding site 3 out of 4 in the Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1) within 5.0Å range: probe atom residue distance (Å) B Occ A:F501 b:63.2 occ:1.00 F21 A:Q4O501 0.0 63.2 1.0 C20 A:Q4O501 1.4 63.4 1.0 O19 A:Q4O501 2.2 60.2 1.0 F22 A:Q4O501 2.3 68.5 1.0 C15 A:Q4O501 2.8 51.5 1.0 O A:HOH710 3.1 46.3 1.0 CB A:MET329 3.1 30.8 1.0 C14 A:Q4O501 3.2 46.3 1.0 C A:MET329 3.5 27.7 1.0 O A:HOH672 3.5 41.6 1.0 N A:LEU330 3.6 28.1 1.0 C16 A:Q4O501 3.7 49.8 1.0 O A:MET329 3.8 27.1 1.0 CA A:MET329 3.9 29.7 1.0 F18 A:Q4O501 4.1 53.0 1.0 O A:ILE326 4.1 25.0 1.0 CA A:LEU330 4.2 28.1 1.0 C13 A:Q4O501 4.4 51.0 1.0 CG A:MET329 4.4 36.0 1.0 CD1 A:LEU333 4.6 31.6 1.0 SD A:MET329 4.8 43.8 1.0 C17 A:Q4O501 4.8 47.8 1.0 CG A:LEU330 4.8 35.9 1.0 N A:MET329 4.8 27.9 1.0 CA A:ILE326 4.9 27.1 1.0 CB A:LEU330 4.9 30.9 1.0 C A:ILE326 4.9 26.1 1.0

Fluorine binding site 4 out of 4 in the Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Crystal Structure of Mutant Pparg (C313A) and NCOR2 with An Inverse Agonist (Compound Si-1) within 5.0Å range: probe atom residue distance (Å) B Occ A:F501 b:68.5 occ:1.00 F22 A:Q4O501 0.0 68.5 1.0 C20 A:Q4O501 1.4 63.4 1.0 F21 A:Q4O501 2.3 63.2 1.0 O19 A:Q4O501 2.3 60.2 1.0 O A:HOH710 2.8 46.3 1.0 CB A:MET329 3.4 30.8 1.0 SD A:MET329 3.6 43.8 1.0 C15 A:Q4O501 3.6 51.5 1.0 CB A:ALA292 3.9 41.4 1.0 CG A:MET329 4.0 36.0 1.0 F18 A:Q4O501 4.1 53.0 1.0 C16 A:Q4O501 4.4 49.8 1.0 CA A:ILE326 4.4 27.1 1.0 CD1 A:ILE296 4.5 30.3 1.0 CE1 A:PHE226 4.5 37.5 1.0 CE A:MET329 4.6 42.2 1.0 C14 A:Q4O501 4.6 46.3 1.0 CG1 A:ILE326 4.6 30.9 1.0 CD1 A:PHE226 4.7 37.4 1.0 O A:ILE325 4.7 25.2 1.0 CA A:MET329 4.8 29.7 1.0 CA A:ALA292 4.8 42.9 1.0 O A:ILE326 4.8 25.0 1.0 CG1 A:ILE296 4.9 29.5 1.0 O A:HOH672 4.9 41.6 1.0

D.L.Orsi, S.J.Ferrara, S.Siegel, A.Friberg, L.Bouche, E.Pook, P.Lienau, J.P.Bluck, C.T.Lemke, G.Akcay, T.Stellfeld, H.Meyer, V.Putter, S.J.Holton, D.Korr, I.Jerchel-Furau, C.Pantelidou, C.A.Strathdee, M.Meyerson, K.Eis, J.T.Goldstein. Discovery and Characterization of Orally Bioavailable 4-Chloro-6-Fluoroisophthalamides As Covalent Pparg Inverse-Agonists. Bioorg.Med.Chem. V. 78 17130 2022.
ISSN: ESSN 1464-3391
PubMed: 36542958
DOI: 10.1016/J.BMC.2022.117130