Fluorine in PDB 6dbn: JAK1 with Compound 23

All present enzymatic activity of JAK1 with Compound 23:
2.7.10.2;

The structure of JAK1 with Compound 23, PDB code: 6dbn was solved by F.F.Vajdos, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	37.81 / 2.48
Space group	C 2 2 21
Cell size a, b, c (Å), α, β, γ (°)	45.510, 88.422, 145.914, 90.00, 90.00, 90.00
R / Rfree (%)	18.6 / 26.2

The binding sites of Fluorine atom in the JAK1 with Compound 23 (pdb code 6dbn). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the JAK1 with Compound 23, PDB code: 6dbn:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the JAK1 with Compound 23


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of JAK1 with Compound 23 within 5.0Å range: probe atom residue distance (Å) B Occ A:F4000 b:52.6 occ:1.00 F1 A:G4J4000 0.0 52.6 1.0 C18 A:G4J4000 1.3 53.7 1.0 F2 A:G4J4000 2.1 54.4 1.0 C17 A:G4J4000 2.5 53.7 1.0 C16 A:G4J4000 2.5 54.0 1.0 H20 A:G4J4000 2.8 53.6 0.0 O1 A:G4J4000 2.8 57.2 1.0 O A:GLY882 2.9 61.5 1.0 C15 A:G4J4000 2.9 53.5 1.0 C A:GLY882 3.2 61.8 1.0 C A:GLU883 3.2 73.2 1.0 O A:GLU883 3.3 71.9 1.0 H21 A:G4J4000 3.4 53.6 0.0 H3 A:G4J4000 3.4 53.9 0.0 N A:GLU883 3.4 62.5 1.0 CA A:GLU883 3.4 64.1 1.0 N A:GLY884 3.8 74.7 1.0 CG2 A:VAL889 3.9 51.1 1.0 O A:GLY887 3.9 67.0 1.0 CA A:LYS888 4.0 56.8 1.0 N A:VAL889 4.0 50.0 1.0 N7 A:G4J4000 4.0 48.1 1.0 CA A:GLY882 4.1 53.0 1.0 C A:LYS888 4.2 55.0 1.0 C A:GLY887 4.2 67.2 1.0 N A:LYS888 4.3 58.9 1.0 CB A:VAL889 4.3 51.3 1.0 CA A:GLY884 4.6 76.2 1.0 CA A:VAL889 4.8 48.9 1.0 O A:HOH4166 4.9 60.8 1.0 H2 A:G4J4000 4.9 46.0 0.0 CB A:GLU883 5.0 65.3 1.0

Fluorine binding site 2 out of 2 in the JAK1 with Compound 23


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of JAK1 with Compound 23 within 5.0Å range: probe atom residue distance (Å) B Occ A:F4000 b:54.4 occ:1.00 F2 A:G4J4000 0.0 54.4 1.0 C18 A:G4J4000 1.3 53.7 1.0 F1 A:G4J4000 2.1 52.6 1.0 C16 A:G4J4000 2.5 54.0 1.0 C17 A:G4J4000 2.5 53.7 1.0 H3 A:G4J4000 2.7 53.9 0.0 H21 A:G4J4000 2.8 53.6 0.0 CE A:LYS908 3.3 62.0 1.0 H20 A:G4J4000 3.4 53.6 0.0 CG2 A:VAL889 3.5 51.1 1.0 CD A:LYS908 3.5 56.7 1.0 NZ A:LYS908 3.6 69.4 1.0 C15 A:G4J4000 3.7 53.5 1.0 C A:GLY887 3.9 67.2 1.0 N A:LYS888 4.0 58.9 1.0 OD1 A:ASP1021 4.0 64.0 1.0 O A:GLY887 4.2 67.0 1.0 O A:HOH4166 4.2 60.8 1.0 O1 A:G4J4000 4.2 57.2 1.0 CG A:LYS908 4.2 51.9 1.0 CA A:LYS888 4.3 56.8 1.0 C A:LYS888 4.3 55.0 1.0 CA A:GLY887 4.3 71.2 1.0 H2 A:G4J4000 4.4 46.0 0.0 O A:HOH4168 4.4 52.4 1.0 O A:GLY882 4.5 61.5 1.0 N A:VAL889 4.5 50.0 1.0 N7 A:G4J4000 4.6 48.1 1.0 CB A:VAL889 4.6 51.3 1.0 O A:LYS888 4.6 52.2 1.0 C A:GLU883 4.8 73.2 1.0 O A:HOH4183 4.9 58.3 1.0 CG A:ASP1021 5.0 61.2 1.0 N A:GLY884 5.0 74.7 1.0 O A:GLU883 5.0 71.9 1.0

A.Fensome, C.M.Ambler, E.Arnold, M.E.Banker, M.F.Brown, J.Chrencik, J.D.Clark, M.E.Dowty, I.V.Efremov, A.Flick, B.S.Gerstenberger, A.Gopalsamy, M.M.Hayward, M.Hegen, B.D.Hollingshead, J.Jussif, J.D.Knafels, D.C.Limburg, D.Lin, T.H.Lin, B.S.Pierce, E.Saiah, R.Sharma, P.T.Symanowicz, J.B.Telliez, J.I.Trujillo, F.F.Vajdos, F.Vincent, Z.K.Wan, L.Xing, X.Yang, X.Yang, L.Zhang. Dual Inhibition of TYK2 and JAK1 For the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-Methyl-1 H-Pyrazol-4-Yl)Amino)Pyrimidin-4-Yl)-3, 8-Diazabicyclo[3.2.1]Octan-8-Yl)Methanone (Pf-06700841). J. Med. Chem. V. 61 8597 2018.
ISSN: ISSN 1520-4804
PubMed: 30113844
DOI: 10.1021/ACS.JMEDCHEM.8B00917