Chlorine 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:

Fluorine

(F)

4 atoms

The binding sites of Chlorine 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 Chlorine atom.
In total 4 binding sites of Chlorine where determined in the Egfr(T790M/V948R) in Complex with A Macrocyclic Inhibitor, PDB code: 7u98:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine 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 Chlorine with other atoms in the Cl 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:Cl1101 b:68.2 occ:1.00 CL04 A:M1O1101 0.0 68.2 1.0 C03 A:M1O1101 1.8 65.4 1.0 C02 A:M1O1101 2.7 75.1 1.0 C05 A:M1O1101 2.8 65.7 1.0 F01 A:M1O1101 3.0 65.9 1.0 SD A:MET790 3.6 84.5 1.0 CB A:LYS745 3.8 53.3 1.0 CG A:MET790 3.9 68.3 1.0 O A:LEU788 3.9 65.9 1.0 CB A:MET790 4.0 50.1 1.0 C27 A:M1O1101 4.0 73.5 1.0 CE A:MET790 4.1 74.1 1.0 C06 A:M1O1101 4.1 66.6 1.0 N A:LYS745 4.3 84.7 1.0 CB A:LEU788 4.4 53.7 1.0 C A:LEU788 4.4 68.3 1.0 N A:MET790 4.5 56.3 1.0 C26 A:M1O1101 4.6 58.7 1.0 O A:ALA743 4.6 59.3 1.0 CA A:LYS745 4.7 82.0 1.0 CD A:LYS745 4.8 62.5 1.0 C A:ILE789 4.8 53.9 1.0 CA A:MET790 4.9 52.4 1.0 CG A:LYS745 4.9 63.2 1.0 N A:ILE789 4.9 71.1 1.0 C A:ILE744 4.9 73.7 1.0 C A:ALA743 5.0 58.1 1.0

Chlorine 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 Chlorine with other atoms in the Cl 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:Cl1101 b:105.6 occ:1.00 CL04 B:M1O1101 0.0 105.6 1.0 C03 B:M1O1101 1.8 90.7 1.0 C02 B:M1O1101 2.7 98.7 1.0 C05 B:M1O1101 2.7 89.6 1.0 F01 B:M1O1101 3.0 101.8 1.0 CG B:MET790 3.4 72.1 1.0 N B:MET790 3.5 60.5 1.0 O B:LEU788 3.5 83.0 1.0 O B:ALA743 3.6 74.3 1.0 N B:LYS745 3.8 65.6 1.0 C B:LEU788 3.8 81.3 1.0 C B:ILE789 3.9 58.6 1.0 CA B:ILE789 3.9 77.1 1.0 N B:ILE789 3.9 73.8 1.0 C B:ALA743 4.0 76.8 1.0 CB B:MET790 4.0 64.0 1.0 C27 B:M1O1101 4.0 91.6 1.0 C06 B:M1O1101 4.1 88.0 1.0 CA B:ILE744 4.1 66.8 1.0 N B:ILE744 4.2 66.1 1.0 CB B:LYS745 4.2 83.1 1.0 C B:ILE744 4.2 65.4 1.0 SD B:MET790 4.3 104.2 1.0 CA B:MET790 4.4 66.4 1.0 CB B:LEU788 4.4 79.8 1.0 CB B:ALA743 4.5 83.1 1.0 C26 B:M1O1101 4.6 85.4 1.0 CA B:LYS745 4.6 86.2 1.0 O B:ILE789 4.7 58.8 1.0 CA B:LEU788 4.7 80.6 1.0 CA B:ALA743 4.9 75.3 1.0

Chlorine 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 Chlorine with other atoms in the Cl 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:Cl1101 b:66.1 occ:1.00 CL04 C:M1O1101 0.0 66.1 1.0 C03 C:M1O1101 1.7 59.5 1.0 C02 C:M1O1101 2.7 75.7 1.0 C05 C:M1O1101 2.7 68.9 1.0 F01 C:M1O1101 2.9 80.2 1.0 CB C:LYS745 3.7 78.9 1.0 O C:LEU788 3.7 86.7 1.0 SD C:MET790 3.8 79.9 1.0 N C:LYS745 3.9 64.0 1.0 CG C:MET790 4.0 55.6 1.0 C27 C:M1O1101 4.0 85.1 1.0 CB C:MET790 4.0 51.1 1.0 C06 C:M1O1101 4.1 76.5 1.0 O C:ALA743 4.1 65.9 1.0 C C:LEU788 4.2 81.4 1.0 N C:MET790 4.3 66.5 1.0 CA C:LYS745 4.4 77.1 1.0 C C:ILE744 4.5 73.5 1.0 CB C:LEU788 4.5 64.5 1.0 C C:ALA743 4.5 63.3 1.0 C26 C:M1O1101 4.6 84.1 1.0 C C:ILE789 4.6 57.0 1.0 CA C:ILE744 4.7 65.2 1.0 N C:ILE789 4.7 72.0 1.0 N C:ILE744 4.7 63.1 1.0 CA C:MET790 4.8 55.8 1.0 CB C:ALA743 4.8 65.8 1.0 CA C:ILE789 4.8 59.4 1.0 CG C:LYS745 4.9 82.6 1.0

Chlorine 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 Chlorine with other atoms in the Cl 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:Cl1101 b:69.6 occ:1.00 CL04 D:M1O1101 0.0 69.6 1.0 C03 D:M1O1101 1.8 85.1 1.0 C02 D:M1O1101 2.7 82.5 1.0 C05 D:M1O1101 2.8 83.9 1.0 F01 D:M1O1101 3.0 85.9 1.0 CG D:MET790 3.3 91.9 1.0 SD D:MET790 3.9 129.0 1.0 O D:LEU788 4.0 84.7 1.0 C27 D:M1O1101 4.1 81.8 1.0 CB D:MET790 4.1 72.4 1.0 N D:MET790 4.1 74.8 1.0 C06 D:M1O1101 4.1 76.0 1.0 O D:ALA743 4.2 72.1 1.0 CB D:LYS745 4.2 79.6 1.0 N D:LYS745 4.4 87.6 1.0 CB D:ALA743 4.4 65.9 1.0 C D:ALA743 4.5 70.0 1.0 C D:LEU788 4.5 87.3 1.0 C26 D:M1O1101 4.6 82.5 1.0 C D:ILE789 4.6 72.2 1.0 CA D:MET790 4.7 73.4 1.0 N D:ILE744 4.8 84.6 1.0 C D:ILE744 4.8 92.6 1.0 CA D:ILE789 4.9 72.7 1.0 N D:ILE789 4.9 89.7 1.0 CB D:LEU788 4.9 70.9 1.0 CE D:MET790 4.9 84.3 1.0 CA D:ILE744 4.9 92.0 1.0 CA D:LYS745 5.0 93.8 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