Fluorine in PDB 4g9c: Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor

All present enzymatic activity of Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor:
2.7.11.1;

The structure of Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor, PDB code: 4g9c was solved by W.C.Voegtli, H.L.Sturgis, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	29.76 / 3.50
Space group	P 41 21 2
Cell size a, b, c (Å), α, β, γ (°)	107.050, 107.050, 161.850, 90.00, 90.00, 90.00
R / Rfree (%)	27.2 / 30.3

The binding sites of Fluorine atom in the Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor (pdb code 4g9c). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor, PDB code: 4g9c:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F801 b:37.7 occ:1.00 F9 A:0WP801 0.0 37.7 1.0 C8 A:0WP801 1.4 36.4 1.0 C2 A:0WP801 2.4 36.4 1.0 C7 A:0WP801 2.4 35.6 1.0 C1 A:0WP801 2.8 36.7 1.0 N12 A:0WP801 2.9 35.2 1.0 CB A:ALA481 3.3 47.4 1.0 OG1 A:THR529 3.5 34.9 1.0 O A:ALA481 3.5 48.4 1.0 C A:ALA481 3.6 49.0 1.0 O3 A:0WP801 3.6 37.7 1.0 N A:LYS483 3.6 61.6 1.0 C4 A:0WP801 3.6 35.9 1.0 C6 A:0WP801 3.7 34.4 1.0 O A:ILE527 3.8 43.1 1.0 CB A:LYS483 3.8 64.3 1.0 C A:VAL482 4.0 57.9 1.0 N A:VAL482 4.0 51.2 1.0 C24 A:0WP801 4.0 34.0 1.0 CA A:ALA481 4.1 47.7 1.0 CG1 A:VAL471 4.1 64.1 1.0 C5 A:0WP801 4.1 35.6 1.0 CA A:LYS483 4.3 65.5 1.0 CA A:VAL482 4.3 53.9 1.0 N A:THR529 4.3 35.1 1.0 CG2 A:THR529 4.3 32.7 1.0 CB A:THR529 4.4 34.0 1.0 CG2 A:VAL471 4.5 63.0 1.0 O A:VAL482 4.6 58.8 1.0 F10 A:0WP801 4.7 38.6 1.0 C25 A:0WP801 4.7 33.7 1.0 C29 A:0WP801 4.8 34.0 1.0 C A:ILE527 4.9 42.7 1.0 CB A:VAL471 5.0 64.1 1.0 CG A:LYS483 5.0 64.9 1.0 CA A:THR529 5.0 34.6 1.0

Fluorine binding site 2 out of 4 in the Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F801 b:38.6 occ:1.00 F10 A:0WP801 0.0 38.6 1.0 C4 A:0WP801 1.3 35.9 1.0 C2 A:0WP801 2.4 36.4 1.0 C5 A:0WP801 2.4 35.6 1.0 O15 A:0WP801 2.5 35.5 1.0 N11 A:0WP801 2.8 36.2 1.0 C1 A:0WP801 2.8 36.7 1.0 C13 A:0WP801 2.9 35.0 1.0 O3 A:0WP801 3.0 37.7 1.0 CA A:PHE595 3.4 53.2 1.0 C8 A:0WP801 3.6 36.4 1.0 O A:ASP594 3.6 46.8 1.0 N A:PHE595 3.7 50.1 1.0 C6 A:0WP801 3.7 34.4 1.0 C A:ASP594 3.7 46.7 1.0 CD2 A:PHE595 3.7 52.4 1.0 CD2 A:LEU514 3.7 23.5 1.0 N12 A:0WP801 3.7 35.2 1.0 C14 A:0WP801 4.0 34.1 1.0 C7 A:0WP801 4.1 35.6 1.0 CG A:PHE595 4.2 51.8 1.0 N A:ASP594 4.2 42.1 1.0 CB A:PHE595 4.2 52.5 1.0 CE2 A:PHE595 4.4 53.0 1.0 C A:PHE595 4.4 55.7 1.0 CA A:ASP594 4.6 44.5 1.0 O A:PHE595 4.6 56.1 1.0 F9 A:0WP801 4.7 37.7 1.0 C20 A:0WP801 4.8 33.9 1.0 C24 A:0WP801 4.8 34.0 1.0 C16 A:0WP801 4.8 34.4 1.0 CE A:LYS483 5.0 65.0 1.0 CG2 A:THR529 5.0 32.7 1.0 C A:GLY593 5.0 40.1 1.0

Fluorine binding site 3 out of 4 in the Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:F801 b:30.2 occ:1.00 F9 B:0WP801 0.0 30.2 1.0 C8 B:0WP801 1.4 30.3 1.0 C2 B:0WP801 2.4 30.2 1.0 C7 B:0WP801 2.4 31.0 1.0 C1 B:0WP801 2.8 29.1 1.0 N12 B:0WP801 3.0 29.1 1.0 CB B:ALA481 3.2 45.0 1.0 OG1 B:THR529 3.3 31.3 1.0 O B:ALA481 3.5 47.4 1.0 C B:ALA481 3.6 46.5 1.0 C4 B:0WP801 3.7 31.5 1.0 C6 B:0WP801 3.7 32.0 1.0 O3 B:0WP801 3.7 28.4 1.0 N B:LYS483 3.8 59.9 1.0 O B:ILE527 3.9 39.8 1.0 CB B:LYS483 4.0 62.9 1.0 CA B:ALA481 4.0 45.0 1.0 N B:VAL482 4.1 48.0 1.0 C24 B:0WP801 4.1 29.7 1.0 CG1 B:VAL471 4.1 60.9 1.0 C B:VAL482 4.1 55.5 1.0 C5 B:0WP801 4.2 32.5 1.0 N B:THR529 4.3 31.1 1.0 CG2 B:THR529 4.3 31.6 1.0 CB B:THR529 4.3 30.1 1.0 CA B:VAL482 4.4 50.9 1.0 CA B:LYS483 4.5 64.0 1.0 CG2 B:VAL471 4.6 61.3 1.0 F10 B:0WP801 4.8 32.9 1.0 O B:VAL482 4.8 57.2 1.0 C25 B:0WP801 4.8 30.7 1.0 CA B:THR529 4.9 30.7 1.0 C29 B:0WP801 4.9 30.2 1.0 N B:ALA481 5.0 44.1 1.0 CB B:VAL471 5.0 60.7 1.0

Fluorine binding site 4 out of 4 in the Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Human B-Raf Kinase Domain Bound to A Type II Pyrazolopyridine Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:F801 b:32.9 occ:1.00 F10 B:0WP801 0.0 32.9 1.0 C4 B:0WP801 1.3 31.5 1.0 C2 B:0WP801 2.4 30.2 1.0 C5 B:0WP801 2.4 32.5 1.0 O15 B:0WP801 2.4 35.0 1.0 N11 B:0WP801 2.8 33.4 1.0 C1 B:0WP801 2.8 29.1 1.0 C13 B:0WP801 2.9 33.5 1.0 O3 B:0WP801 3.0 28.4 1.0 CD2 B:LEU514 3.4 22.5 1.0 CD2 B:PHE595 3.5 40.3 1.0 CA B:PHE595 3.7 48.2 1.0 C8 B:0WP801 3.7 30.3 1.0 C6 B:0WP801 3.7 32.0 1.0 N B:PHE595 3.8 46.1 1.0 N12 B:0WP801 3.8 29.1 1.0 C B:ASP594 3.8 44.2 1.0 O B:ASP594 3.8 45.1 1.0 CE2 B:PHE595 3.9 39.7 1.0 N B:ASP594 4.1 39.2 1.0 CG B:PHE595 4.1 41.9 1.0 C7 B:0WP801 4.2 31.0 1.0 C14 B:0WP801 4.2 32.9 1.0 CB B:PHE595 4.4 45.1 1.0 CA B:ASP594 4.6 42.0 1.0 C B:PHE595 4.8 51.7 1.0 F9 B:0WP801 4.8 30.2 1.0 C B:GLY593 4.8 37.4 1.0 CG2 B:THR529 4.8 31.6 1.0 CZ B:PHE595 4.9 39.8 1.0 CG B:LEU514 4.9 21.5 1.0 C24 B:0WP801 4.9 29.7 1.0 CA B:GLY593 4.9 34.7 1.0 O B:PHE595 4.9 52.4 1.0

S.Wenglowsky, D.Moreno, E.R.Laird, S.L.Gloor, L.Ren, T.Risom, J.Rudolph, H.L.Sturgis, W.C.Voegtli. Pyrazolopyridine Inhibitors of B-Raf(V600E). Part 4: Rational Design and Kinase Selectivity Profile of Cell Potent Type II Inhibitors. Bioorg.Med.Chem.Lett. V. 22 6237 2012.
ISSN: ISSN 0960-894X
PubMed: 22954737
DOI: 10.1016/J.BMCL.2012.08.007