Fluorine in PDB 6v66: Egfr(T790M/V948R) in Complex with LN2899

All present enzymatic activity of Egfr(T790M/V948R) in Complex with LN2899:
2.7.10.1;

The structure of Egfr(T790M/V948R) in Complex with LN2899, PDB code: 6v66 was solved by D.E.Heppner, M.J.Eck, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	85.26 / 1.79
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	71.480, 102.448, 87.422, 90.00, 102.78, 90.00
R / Rfree (%)	18.5 / 22.6

The structure of Egfr(T790M/V948R) in Complex with LN2899 also contains other interesting chemical elements:

Chlorine

(Cl)

4 atoms

The binding sites of Fluorine atom in the Egfr(T790M/V948R) in Complex with LN2899 (pdb code 6v66). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Egfr(T790M/V948R) in Complex with LN2899, PDB code: 6v66:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Egfr(T790M/V948R) in Complex with LN2899


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Egfr(T790M/V948R) in Complex with LN2899 within 5.0Å range: probe atom residue distance (Å) B Occ D:F1203 b:32.3 occ:1.00 F34 D:QP11203 0.0 32.3 1.0 C06 D:QP11203 1.4 23.8 1.0 C09 D:QP11203 2.5 22.8 1.0 C03 D:QP11203 2.5 26.7 1.0 CB D:LEU788 3.1 23.4 1.0 C D:LEU788 3.4 22.2 1.0 O D:LEU788 3.4 22.4 1.0 CG D:MET790 3.6 25.7 1.0 N D:ILE789 3.7 20.6 1.0 C D:ILE789 3.8 21.8 1.0 CA D:LEU788 3.8 28.2 1.0 C11 D:QP11203 3.8 22.6 1.0 CD1 D:LEU777 3.9 15.3 1.0 C01 D:QP11203 3.9 26.1 1.0 CB D:MET790 3.9 24.9 1.0 N D:MET790 3.9 21.7 1.0 CA D:ILE789 4.1 19.2 1.0 O D:ILE789 4.1 18.7 1.0 CE D:MET790 4.2 20.7 1.0 SD D:MET790 4.2 37.9 1.0 CD1 D:LEU788 4.2 22.8 1.0 CG D:LEU788 4.2 21.2 1.0 C13 D:QP11203 4.4 23.5 1.0 CB D:LYS745 4.4 24.0 1.0 CA D:MET790 4.5 20.7 1.0 O D:ALA743 4.6 26.2 1.0 N D:LYS745 4.7 24.1 1.0 N D:LEU788 4.9 26.6 1.0

Fluorine binding site 2 out of 4 in the Egfr(T790M/V948R) in Complex with LN2899


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Egfr(T790M/V948R) in Complex with LN2899 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1202 b:16.4 occ:1.00 F34 A:QP11202 0.0 16.4 1.0 C06 A:QP11202 1.3 15.5 1.0 C09 A:QP11202 2.5 11.5 1.0 C03 A:QP11202 2.5 20.0 1.0 C A:LEU788 2.8 14.1 1.0 N A:ILE789 2.9 13.6 1.0 CB A:LEU788 3.0 17.4 1.0 O A:LEU788 3.0 14.7 1.0 C A:ILE789 3.1 14.9 1.0 CG A:MET790 3.3 18.1 1.0 N A:MET790 3.4 13.9 1.0 CA A:ILE789 3.4 16.5 1.0 O A:ILE789 3.5 16.8 1.0 CA A:LEU788 3.5 16.1 1.0 CD1 A:LEU777 3.6 13.0 1.0 CB A:MET790 3.7 12.5 1.0 C01 A:QP11202 3.8 15.6 1.0 C11 A:QP11202 3.8 15.3 1.0 CA A:MET790 4.1 16.2 1.0 SD A:MET790 4.2 27.9 1.0 C13 A:QP11202 4.3 14.0 1.0 CG A:LEU788 4.4 17.4 1.0 O A:ALA743 4.4 15.9 1.0 N A:LYS745 4.5 12.6 1.0 CD1 A:LEU788 4.6 18.5 1.0 N A:LEU788 4.6 17.9 1.0 CB A:LYS745 4.7 12.3 1.0 CE A:MET790 4.8 16.0 1.0 CB A:ILE789 4.9 19.9 1.0

Fluorine binding site 3 out of 4 in the Egfr(T790M/V948R) in Complex with LN2899


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Egfr(T790M/V948R) in Complex with LN2899 within 5.0Å range: probe atom residue distance (Å) B Occ B:F1202 b:26.3 occ:1.00 F34 B:QP11202 0.0 26.3 1.0 C06 B:QP11202 1.4 24.6 1.0 C03 B:QP11202 2.5 26.2 1.0 C09 B:QP11202 2.5 21.5 1.0 CB B:LEU788 3.0 17.5 1.0 C B:LEU788 3.0 17.9 1.0 O B:LEU788 3.1 16.8 1.0 N B:ILE789 3.3 15.6 1.0 CG B:MET790 3.3 25.5 1.0 C B:ILE789 3.6 19.1 1.0 CA B:LEU788 3.6 17.8 1.0 CA B:ILE789 3.8 17.1 1.0 N B:MET790 3.8 20.1 1.0 CD1 B:LEU777 3.8 18.4 1.0 C01 B:QP11202 3.8 26.2 1.0 C11 B:QP11202 3.9 20.5 1.0 O B:ILE789 3.9 20.2 1.0 CB B:MET790 3.9 20.3 1.0 SD B:MET790 4.0 35.8 1.0 CG B:LEU788 4.3 21.4 1.0 C13 B:QP11202 4.4 24.2 1.0 CD1 B:LEU788 4.4 23.8 1.0 CA B:MET790 4.4 18.2 1.0 CB B:LYS745 4.5 17.9 1.0 N B:LYS745 4.5 19.0 1.0 O B:ALA743 4.5 18.9 1.0 CE B:MET790 4.6 23.2 1.0 N B:LEU788 4.7 19.3 1.0 O B:HOH1478 4.7 35.3 1.0

Fluorine binding site 4 out of 4 in the Egfr(T790M/V948R) in Complex with LN2899


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Egfr(T790M/V948R) in Complex with LN2899 within 5.0Å range: probe atom residue distance (Å) B Occ C:F1101 b:22.5 occ:1.00 F34 C:QP11101 0.0 22.5 1.0 C06 C:QP11101 1.3 21.4 1.0 C03 C:QP11101 2.5 23.1 1.0 C09 C:QP11101 2.5 22.4 1.0 C C:LEU788 2.9 19.9 1.0 CB C:LEU788 3.0 17.1 1.0 N C:ILE789 3.0 15.0 1.0 O C:LEU788 3.0 15.9 1.0 C C:ILE789 3.4 15.7 1.0 CD1 C:LEU777 3.5 16.1 1.0 CA C:ILE789 3.5 14.8 1.0 CA C:LEU788 3.5 16.7 1.0 CG C:MET790 3.6 23.3 1.0 N C:MET790 3.6 16.0 1.0 O C:ILE789 3.8 17.7 1.0 C01 C:QP11101 3.8 22.7 1.0 C11 C:QP11101 3.8 21.2 1.0 CB C:MET790 3.9 18.1 1.0 SD C:MET790 4.2 28.9 1.0 C13 C:QP11101 4.3 22.2 1.0 CA C:MET790 4.3 15.2 1.0 CG C:LEU788 4.4 19.7 1.0 O C:ALA743 4.4 18.2 1.0 N C:LYS745 4.4 18.4 1.0 CB C:LYS745 4.4 24.6 1.0 CD1 C:LEU788 4.5 21.3 1.0 N C:LEU788 4.7 18.3 1.0 CG C:LEU777 5.0 15.2 1.0 O C:HOH1390 5.0 36.8 1.0

D.E.Heppner, M.Gunther, F.Wittlinger, S.A.Laufer, M.J.Eck. Structural Basis For Egfr Mutant Inhibition By Trisubstituted Imidazole Inhibitors. J.Med.Chem. 2020.
ISSN: ISSN 0022-2623
PubMed: 32243152
DOI: 10.1021/ACS.JMEDCHEM.0C00200