Fluorine in PDB 4cqe: B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor

The structure of B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor, PDB code: 4cqe was solved by E.Casale, M.Fasolini, M.Pulici, G.Traquandi, C.Marchionni, M.Modugno, R.Lupi, N.Amboldi, N.Colombo, L.Corti, F.Gasparri, W.Pastori, A.Scolaro, D.Donati, E.Felder, A.Galvani, A.Isacchi, E.Pesenti, M.Ciomei, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	30.00 / 2.30
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	52.605, 105.943, 109.889, 90.00, 90.00, 90.00
R / Rfree (%)	20.763 / 25.519

The binding sites of Fluorine atom in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor (pdb code 4cqe). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor, PDB code: 4cqe:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F1721 b:33.5 occ:1.00 F18 A:CQE1721 0.0 33.5 1.0 C13 A:CQE1721 1.4 33.9 1.0 C12 A:CQE1721 2.3 32.5 1.0 C14 A:CQE1721 2.4 35.4 1.0 O10 A:CQE1721 2.7 36.0 1.0 S9 A:CQE1721 2.9 32.5 1.0 N A:ASP594 3.2 37.3 1.0 CE2 A:PHE595 3.2 45.3 1.0 N8 A:CQE1721 3.3 30.3 1.0 CD2 A:PHE595 3.4 45.0 1.0 CA A:GLY593 3.4 33.7 1.0 C A:GLY593 3.6 32.0 1.0 C17 A:CQE1721 3.6 34.9 1.0 C15 A:CQE1721 3.7 35.4 1.0 CZ A:PHE595 3.8 47.0 1.0 N A:PHE595 3.9 40.6 1.0 O A:ILE592 4.1 33.0 1.0 CG A:PHE595 4.1 46.5 1.0 C16 A:CQE1721 4.1 37.0 1.0 CA A:ASP594 4.2 38.6 1.0 CD2 A:LEU514 4.2 29.5 1.0 C5 A:CQE1721 4.3 30.4 1.0 CB A:LEU514 4.3 34.0 1.0 O11 A:CQE1721 4.3 31.3 1.0 CE1 A:PHE595 4.5 48.7 1.0 CD2 A:LEU505 4.5 44.2 1.0 O A:GLY593 4.5 31.0 1.0 C A:ASP594 4.6 37.7 1.0 N A:GLY593 4.6 34.0 1.0 CD1 A:PHE595 4.6 47.6 1.0 N A:GLY596 4.8 57.2 1.0 C A:ILE592 4.8 32.9 1.0 CG A:LEU514 4.8 30.4 1.0 CA A:PHE595 4.9 46.1 1.0 C4 A:CQE1721 4.9 29.6 1.0

Fluorine binding site 2 out of 6 in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F1721 b:41.0 occ:1.00 F19 A:CQE1721 0.0 41.0 1.0 C16 A:CQE1721 1.4 37.0 1.0 C15 A:CQE1721 2.4 35.4 1.0 C17 A:CQE1721 2.5 34.9 1.0 CD1 A:PHE516 3.2 35.0 1.0 CB A:PHE516 3.2 32.6 1.0 CG2 A:ILE527 3.2 44.2 1.0 CG2 A:THR529 3.2 27.9 1.0 CA A:PHE516 3.3 31.8 1.0 CG A:PHE516 3.7 35.5 1.0 C14 A:CQE1721 3.7 35.4 1.0 C12 A:CQE1721 3.7 32.5 1.0 O A:VAL528 3.9 32.3 1.0 CD1 A:LEU505 3.9 45.7 1.0 N A:PHE516 4.1 32.4 1.0 C13 A:CQE1721 4.2 33.9 1.0 CB A:LEU505 4.2 43.1 1.0 CB A:THR529 4.4 28.4 1.0 CE1 A:PHE516 4.4 34.6 1.0 CG A:LEU505 4.4 44.8 1.0 C A:PHE516 4.5 35.4 1.0 O A:LEU515 4.6 32.3 1.0 CD2 A:LEU505 4.6 44.2 1.0 N A:MET517 4.6 33.8 1.0 C A:VAL528 4.6 30.9 1.0 C A:LEU515 4.7 31.7 1.0 CB A:ILE527 4.8 40.9 1.0 CA A:THR529 4.8 30.7 1.0

Fluorine binding site 3 out of 6 in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F1721 b:31.4 occ:1.00 F7 A:CQE1721 0.0 31.4 1.0 C6 A:CQE1721 1.3 30.4 1.0 C5 A:CQE1721 2.3 30.4 1.0 C1 A:CQE1721 2.3 34.5 1.0 N8 A:CQE1721 2.5 30.3 1.0 N21 A:CQE1721 2.7 37.7 1.0 C20 A:CQE1721 2.7 35.9 1.0 O A:HOH2011 3.0 47.4 1.0 N A:ASP594 3.3 37.3 1.0 C4 A:CQE1721 3.5 29.6 1.0 C2 A:CQE1721 3.6 32.5 1.0 CZ A:PHE583 3.7 47.4 1.0 CA A:ASP594 3.7 38.6 1.0 CB A:ASP594 3.7 40.1 1.0 CE2 A:PHE583 3.8 49.7 1.0 C22 A:CQE1721 3.8 43.3 1.0 C24 A:CQE1721 3.9 35.0 1.0 C3 A:CQE1721 4.0 32.0 1.0 S9 A:CQE1721 4.1 32.5 1.0 C A:GLY593 4.1 32.0 1.0 CD2 A:LEU514 4.2 29.5 1.0 CA A:GLY593 4.2 33.7 1.0 CG A:ASP594 4.5 46.4 1.0 C25 A:CQE1721 4.6 52.9 1.0 S23 A:CQE1721 4.6 36.4 1.0 OD1 A:ASP594 4.7 42.7 1.0 CE A:LYS483 4.7 44.1 1.0 C32 A:CQE1721 4.8 31.4 1.0 O11 A:CQE1721 4.8 31.3 1.0 O10 A:CQE1721 4.8 36.0 1.0 C31 A:CQE1721 4.8 31.0 1.0 NZ A:LYS483 5.0 50.5 1.0 CE1 A:PHE583 5.0 45.2 1.0

Fluorine binding site 4 out of 6 in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:F1721 b:42.3 occ:1.00 F18 B:CQE1721 0.0 42.3 1.0 C13 B:CQE1721 1.3 42.9 1.0 C12 B:CQE1721 2.4 41.6 1.0 C14 B:CQE1721 2.4 45.2 1.0 O10 B:CQE1721 2.9 34.0 1.0 S9 B:CQE1721 3.0 36.5 1.0 N B:ASP594 3.1 48.2 1.0 CA B:GLY593 3.2 36.7 1.0 C B:GLY593 3.4 41.6 1.0 N8 B:CQE1721 3.4 36.4 1.0 CE1 B:PHE595 3.4 67.8 1.0 CD1 B:PHE595 3.5 70.7 1.0 C17 B:CQE1721 3.6 40.9 1.0 C15 B:CQE1721 3.6 45.6 1.0 O B:ILE592 3.9 35.1 1.0 N B:PHE595 4.1 55.2 1.0 C16 B:CQE1721 4.1 47.9 1.0 CA B:ASP594 4.1 48.4 1.0 CB B:LEU514 4.2 31.7 1.0 CZ B:PHE595 4.2 64.5 1.0 CD2 B:LEU514 4.2 29.3 1.0 O B:GLY593 4.3 36.8 1.0 CG B:PHE595 4.3 68.4 1.0 N B:GLY593 4.3 37.4 1.0 C5 B:CQE1721 4.4 37.0 1.0 O11 B:CQE1721 4.5 38.3 1.0 CD2 B:LEU505 4.5 36.8 1.0 C B:ILE592 4.5 36.9 1.0 C B:ASP594 4.6 49.6 1.0 CG B:LEU514 4.8 30.8 1.0 CE2 B:PHE595 4.9 68.6 1.0 CD2 B:PHE595 4.9 69.1 1.0

Fluorine binding site 5 out of 6 in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:F1721 b:47.9 occ:1.00 F19 B:CQE1721 0.0 47.9 1.0 C16 B:CQE1721 1.3 47.9 1.0 C17 B:CQE1721 2.3 40.9 1.0 C15 B:CQE1721 2.3 45.6 1.0 CA B:PHE516 3.2 37.8 1.0 CB B:PHE516 3.3 37.0 1.0 CG2 B:THR529 3.4 41.2 1.0 CD1 B:PHE516 3.4 47.1 1.0 C12 B:CQE1721 3.6 41.6 1.0 C14 B:CQE1721 3.6 45.2 1.0 CG2 B:ILE527 3.7 42.0 1.0 CG B:PHE516 3.8 44.5 1.0 N B:PHE516 3.8 35.7 1.0 CD1 B:LEU505 3.9 44.5 1.0 O B:VAL528 4.0 43.5 1.0 CB B:THR529 4.0 40.4 1.0 C13 B:CQE1721 4.1 42.9 1.0 CB B:LEU505 4.3 40.9 1.0 CD2 B:LEU505 4.4 36.8 1.0 C B:LEU515 4.4 34.0 1.0 CG B:LEU505 4.4 44.9 1.0 O B:LEU515 4.4 34.0 1.0 C B:PHE516 4.5 40.3 1.0 CE1 B:PHE516 4.6 45.3 1.0 CA B:THR529 4.6 40.5 1.0 C B:VAL528 4.7 43.7 1.0 N B:MET517 4.7 40.0 1.0

Fluorine binding site 6 out of 6 in the B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of B-Raf Kinase V600E Mutant in Complex with A Diarylthiazole B-Raf Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:F1721 b:41.6 occ:1.00 F7 B:CQE1721 0.0 41.6 1.0 C6 B:CQE1721 1.3 37.7 1.0 C5 B:CQE1721 2.3 37.0 1.0 C1 B:CQE1721 2.4 41.2 1.0 N8 B:CQE1721 2.5 36.4 1.0 N21 B:CQE1721 2.8 45.4 1.0 C20 B:CQE1721 2.8 44.0 1.0 O B:HOH2006 2.9 48.6 1.0 N B:ASP594 3.2 48.2 1.0 CB B:ASP594 3.4 51.7 1.0 CZ B:PHE583 3.5 53.0 1.0 CA B:ASP594 3.5 48.4 1.0 C4 B:CQE1721 3.5 39.3 1.0 C2 B:CQE1721 3.6 42.0 1.0 CE2 B:PHE583 3.8 55.9 1.0 NZ B:LYS483 3.8 56.3 1.0 C22 B:CQE1721 3.9 51.8 1.0 CG B:ASP594 4.0 56.2 1.0 C24 B:CQE1721 4.0 47.7 1.0 S9 B:CQE1721 4.0 36.5 1.0 C3 B:CQE1721 4.0 39.1 1.0 C B:GLY593 4.1 41.6 1.0 OD2 B:ASP594 4.2 55.3 1.0 CD2 B:LEU514 4.3 29.3 1.0 CE B:LYS483 4.3 56.0 1.0 CA B:GLY593 4.3 36.7 1.0 C26 B:CQE1721 4.5 62.3 1.0 OD1 B:ASP594 4.7 52.4 1.0 O11 B:CQE1721 4.7 38.3 1.0 O10 B:CQE1721 4.7 34.0 1.0 CE1 B:PHE583 4.7 50.0 1.0 C25 B:CQE1721 4.8 57.7 1.0 S23 B:CQE1721 4.8 48.8 1.0 C32 B:CQE1721 4.8 43.5 1.0 C31 B:CQE1721 4.9 44.6 1.0

M.Pulici, G.Traquandi, C.Marchionni, M.Modugno, R.Lupi, N.Amboldi, E.Casale, N.Colombo, L.Corti, M.Fasolini, F.Gasparri, W.Pastori, A.Scolaro, D.Donati, E.Felder, A.Galvani, A.Isacchi, E.Pesenti, M.Ciomei. Optimization of Diarylthiazole B-Raf Inhibitors: Identification of A Compound Endowed with High Oral Antitumor Activity, Mitigated Herg Inhibition, and Low Paradoxical Effect. Chemmedchem 2014.
ISSN: ESSN 1860-7187
PubMed: 25430902
DOI: 10.1002/CMDC.201402424