Fluorine in PDB 7u98: Egfr(T790M/V948R) in Complex with A Macrocyclic Inhibitor

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

The structure of Egfr(T790M/V948R) in Complex with A Macrocyclic Inhibitor, PDB code: 7u98 was solved by T.S.Beyett, M.J.Eck, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	86.32 / 3.42
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	71.353, 100.923, 88.309, 90, 102.17, 90
R / Rfree (%)	21.5 / 24.4

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

Chlorine

(Cl)

4 atoms

The binding sites of Fluorine atom in the Egfr(T790M/V948R) in Complex with A Macrocyclic Inhibitor (pdb code 7u98). 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 A Macrocyclic Inhibitor, PDB code: 7u98:
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 A Macrocyclic Inhibitor


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 A Macrocyclic Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:65.9 occ:1.00 F01 A:M1O1101 0.0 65.9 1.0 C02 A:M1O1101 1.4 75.1 1.0 C27 A:M1O1101 2.4 73.5 1.0 C03 A:M1O1101 2.4 65.4 1.0 CL04 A:M1O1101 3.0 68.2 1.0 CD2 A:LEU858 3.1 73.2 1.0 OD1 A:ASP855 3.3 86.8 1.0 CD A:LYS745 3.5 62.5 1.0 C26 A:M1O1101 3.6 58.7 1.0 C05 A:M1O1101 3.6 65.7 1.0 C06 A:M1O1101 4.2 66.6 1.0 SD A:MET790 4.2 84.5 1.0 CA A:ASP855 4.3 59.2 1.0 CG A:ASP855 4.3 88.3 1.0 CB A:LYS745 4.4 53.3 1.0 CG A:LEU858 4.4 83.2 1.0 N A:ASP855 4.5 64.5 1.0 CG A:LYS745 4.6 63.2 1.0 CE A:LYS745 4.6 68.9 1.0 OG1 A:THR854 4.6 52.0 1.0 O25 A:M1O1101 4.8 53.9 1.0 CE A:MET790 4.9 74.1 1.0 CB A:ASP855 4.9 74.5 1.0

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


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 A Macrocyclic Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:F1101 b:101.8 occ:1.00 F01 B:M1O1101 0.0 101.8 1.0 C02 B:M1O1101 1.4 98.7 1.0 C03 B:M1O1101 2.4 90.7 1.0 C27 B:M1O1101 2.4 91.6 1.0 CL04 B:M1O1101 3.0 105.6 1.0 C05 B:M1O1101 3.6 89.6 1.0 C26 B:M1O1101 3.7 85.4 1.0 CB B:LYS745 4.0 83.1 1.0 C06 B:M1O1101 4.2 88.0 1.0 CD1 B:LEU788 4.2 61.9 1.0 CB B:LEU788 4.3 79.8 1.0 OD1 B:ASP855 4.3 97.3 1.0 CD B:LYS745 4.4 84.1 1.0 SD B:MET790 4.5 104.2 1.0 CG B:MET790 4.7 72.1 1.0 CG B:LYS745 4.8 71.6 1.0 O25 B:M1O1101 4.8 80.8 1.0 CD1 B:LEU777 4.9 57.6 1.0 CG B:LEU788 5.0 63.9 1.0

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


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 A Macrocyclic Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ C:F1101 b:80.2 occ:1.00 F01 C:M1O1101 0.0 80.2 1.0 C02 C:M1O1101 1.4 75.7 1.0 C27 C:M1O1101 2.4 85.1 1.0 C03 C:M1O1101 2.4 59.5 1.0 CL04 C:M1O1101 2.9 66.1 1.0 C26 C:M1O1101 3.6 84.1 1.0 C05 C:M1O1101 3.7 68.9 1.0 SD C:MET790 3.9 79.9 1.0 CB C:LYS745 4.2 78.9 1.0 C06 C:M1O1101 4.2 76.5 1.0 CG C:LYS745 4.5 82.6 1.0 CE C:LYS745 4.5 84.3 1.0 OD1 C:ASP855 4.6 92.4 1.0 O25 C:M1O1101 4.8 78.3 1.0 OG1 C:THR854 4.8 54.5 1.0 CE C:MET790 4.8 55.0 1.0 CD C:LYS745 4.9 84.2 1.0 CD1 C:LEU788 4.9 71.1 1.0 CA C:ASP855 5.0 64.3 1.0

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


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 A Macrocyclic Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ D:F1101 b:85.9 occ:1.00 F01 D:M1O1101 0.0 85.9 1.0 C02 D:M1O1101 1.4 82.5 1.0 C27 D:M1O1101 2.4 81.8 1.0 C03 D:M1O1101 2.4 85.1 1.0 CL04 D:M1O1101 3.0 69.6 1.0 CD D:LYS745 3.0 96.5 1.0 OD1 D:ASP855 3.2 88.3 1.0 CB D:LYS745 3.4 79.6 1.0 C05 D:M1O1101 3.7 83.9 1.0 C26 D:M1O1101 3.7 82.5 1.0 CG D:LYS745 3.8 88.6 1.0 CE D:LYS745 4.2 83.8 1.0 C06 D:M1O1101 4.2 76.0 1.0 CG D:ASP855 4.4 89.4 1.0 NZ D:LYS745 4.6 75.3 1.0 O25 D:M1O1101 4.8 82.0 1.0 CA D:LYS745 4.8 93.8 1.0 CD1 D:LEU788 4.9 93.5 1.0 C24 D:M1O1101 4.9 74.7 1.0

J.A.Amrhein, T.S.Beyett, W.W.Feng, A.Kramer, J.Weckesser, I.K.Schaeffner, J.K.Rana, P.A.Janne, M.J.Eck, S.Knapp, T.Hanke. Macrocyclization of Quinazoline-Based Egfr Inhibitors Leads to Exclusive Mutant Selectivity For Egfr L858R and DEL19. J.Med.Chem. V. 65 15679 2022.
ISSN: ISSN 0022-2623
PubMed: 36384036
DOI: 10.1021/ACS.JMEDCHEM.2C01041