Fluorine in PDB 2xa4: Inhibitors of JAK2 Kinase Domain

All present enzymatic activity of Inhibitors of JAK2 Kinase Domain:
2.7.1.112; 2.7.10.2;

The structure of Inhibitors of JAK2 Kinase Domain, PDB code: 2xa4 was solved by J.Read, I.Green, H.Pollard, T.Howard, R.Mott, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	33.33 / 2.04
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	43.854, 126.741, 134.342, 90.00, 97.04, 90.00
R / Rfree (%)	19.7 / 24.5

The structure of Inhibitors of JAK2 Kinase Domain also contains other interesting chemical elements:

Chlorine

(Cl)

2 atoms

The binding sites of Fluorine atom in the Inhibitors of JAK2 Kinase Domain (pdb code 2xa4). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Inhibitors of JAK2 Kinase Domain, PDB code: 2xa4:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Inhibitors of JAK2 Kinase Domain


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Inhibitors of JAK2 Kinase Domain within 5.0Å range: probe atom residue distance (Å) B Occ A:F2131 b:36.5 occ:1.00 F23 A:AZ52131 0.0 36.5 1.0 C20 A:AZ52131 1.3 35.0 1.0 C19 A:AZ52131 2.4 34.8 1.0 C21 A:AZ52131 2.4 35.1 1.0 O A:ASN981 3.2 27.4 1.0 C A:ASN981 3.2 27.8 1.0 CA A:ASN981 3.4 28.2 1.0 C A:GLY993 3.5 30.4 1.0 CA A:GLY993 3.6 30.0 1.0 CG A:LEU983 3.6 25.1 1.0 N18 A:AZ52131 3.6 31.9 1.0 N22 A:AZ52131 3.6 33.0 1.0 O A:GLY993 3.7 29.8 1.0 O A:ARG980 3.8 28.1 1.0 N A:ASP994 3.9 31.8 1.0 N A:ILE982 3.9 27.5 1.0 C17 A:AZ52131 4.0 33.9 1.0 CD2 A:LEU983 4.0 25.6 1.0 CD1 A:LEU983 4.1 26.6 1.0 CB A:ASP994 4.1 33.4 1.0 N A:GLY993 4.2 29.2 1.0 C A:ILE982 4.3 27.2 1.0 N A:ASN981 4.4 28.4 1.0 N A:LEU983 4.4 26.6 1.0 CB A:ASN981 4.4 28.4 1.0 OD1 A:ASN981 4.4 31.8 1.0 O A:ILE982 4.5 25.9 1.0 O A:HOH2072 4.5 56.6 1.0 CA A:ILE982 4.5 27.4 1.0 C A:ARG980 4.5 28.6 1.0 CA A:ASP994 4.6 32.7 1.0 CB A:LEU983 4.7 26.7 1.0 CG A:ASN981 5.0 29.3 1.0 CA A:LEU983 5.0 26.3 1.0

Fluorine binding site 2 out of 2 in the Inhibitors of JAK2 Kinase Domain


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Inhibitors of JAK2 Kinase Domain within 5.0Å range: probe atom residue distance (Å) B Occ B:F2132 b:39.1 occ:1.00 F23 B:AZ52132 0.0 39.1 1.0 C20 B:AZ52132 1.3 37.4 1.0 C21 B:AZ52132 2.4 35.7 1.0 C19 B:AZ52132 2.4 38.2 1.0 C B:ASN981 3.2 23.7 1.0 O B:ASN981 3.3 23.1 1.0 CA B:ASN981 3.3 24.0 1.0 N22 B:AZ52132 3.6 35.4 1.0 N18 B:AZ52132 3.6 36.4 1.0 O B:ARG980 3.6 25.1 1.0 C B:GLY993 3.6 28.7 1.0 CG B:LEU983 3.6 23.8 1.0 CA B:GLY993 3.7 27.8 1.0 N B:ILE982 3.8 23.9 1.0 O B:GLY993 3.9 29.9 1.0 N B:ASP994 4.0 29.1 1.0 C17 B:AZ52132 4.0 36.3 1.0 CD1 B:LEU983 4.1 22.0 1.0 CD2 B:LEU983 4.1 24.4 1.0 N B:GLY993 4.2 26.5 1.0 C B:ILE982 4.2 24.1 1.0 CB B:ASP994 4.2 29.7 1.0 N B:ASN981 4.3 24.5 1.0 C B:ARG980 4.4 24.7 1.0 CA B:ILE982 4.4 24.0 1.0 O B:ILE982 4.4 23.9 1.0 CB B:ASN981 4.4 23.8 1.0 N B:LEU983 4.5 24.1 1.0 CA B:ASP994 4.7 29.4 1.0 OD1 B:ASN981 4.7 25.0 1.0 CB B:LEU983 4.8 23.8 1.0

S.Ioannidis, M.L.Lamb, T.Wang, L.Almeida, M.H.Block, A.M.Davies, B.Peng, M.Su, H.Zhang, E.Hoffmann, C.Rivard, I.Green, T.Howard, H.Pollard, J.Read, M.Alimzhanov, G.Bebernitz, K.Bell, M.Ye, D.Huszar, M.Zinda. Discovery of 5-Chloro-N2-[(1S)-1-(5-Fluoropyrimidin-2-Yl) Ethyl]-N4-(5-Methyl-1H-Pyrazol-3-Yl)Pyrimidine-2,4-Diamine (AZD1480) As A Novel Inhibitor of the Jak/Stat Pathway J.Med.Chem. V. 54 262 2011.
ISSN: ISSN 0022-2623
PubMed: 21138246
DOI: 10.1021/JM1011319