Fluorine in PDB 5vam: Braf in Complex with RAF709

All present enzymatic activity of Braf in Complex with RAF709:
2.7.11.1;

The structure of Braf in Complex with RAF709, PDB code: 5vam was solved by M.Mamo, B.A.Appleton, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	30.75 / 2.10
Space group	P 41 21 2
Cell size a, b, c (Å), α, β, γ (°)	109.390, 109.390, 135.980, 90.00, 90.00, 90.00
R / Rfree (%)	19.2 / 22.3

The binding sites of Fluorine atom in the Braf in Complex with RAF709 (pdb code 5vam). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the Braf in Complex with RAF709, PDB code: 5vam:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in the Braf in Complex with RAF709


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Braf in Complex with RAF709 within 5.0Å range: probe atom residue distance (Å) B Occ A:F801 b:35.8 occ:1.00 F33 A:92J801 0.0 35.8 1.0 C30 A:92J801 1.4 30.9 1.0 F31 A:92J801 2.2 30.2 1.0 F32 A:92J801 2.2 33.0 1.0 C27 A:92J801 2.4 28.2 1.0 C28 A:92J801 2.8 25.4 1.0 C A:GLY593 3.5 23.5 1.0 NE2 A:HIS574 3.5 25.1 1.0 O A:GLY593 3.6 20.3 1.0 CA A:GLY593 3.6 20.9 1.0 CD2 A:HIS574 3.6 25.5 1.0 C26 A:92J801 3.6 28.8 1.0 O A:ILE592 3.9 20.5 1.0 N A:GLY593 3.9 20.6 1.0 CG2 A:ILE592 3.9 23.5 1.0 C A:ILE592 4.0 21.7 1.0 N A:ASP594 4.1 23.8 1.0 C23 A:92J801 4.2 23.9 1.0 CD1 A:LEU567 4.4 20.8 1.0 CE1 A:HIS574 4.6 25.2 1.0 CB A:ILE592 4.7 22.1 1.0 CB A:ASP594 4.7 26.8 1.0 CG A:HIS574 4.7 24.8 1.0 C25 A:92J801 4.8 30.1 1.0 CG2 A:ILE513 4.8 15.9 1.0 CA A:ASP594 4.9 24.5 1.0 O29 A:92J801 4.9 24.4 1.0 C24 A:92J801 5.0 27.5 1.0 CA A:ILE592 5.0 18.7 1.0

Fluorine binding site 2 out of 6 in the Braf in Complex with RAF709


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Braf in Complex with RAF709 within 5.0Å range: probe atom residue distance (Å) B Occ A:F801 b:33.0 occ:1.00 F32 A:92J801 0.0 33.0 1.0 C30 A:92J801 1.3 30.9 1.0 F31 A:92J801 2.2 30.2 1.0 F33 A:92J801 2.2 35.8 1.0 C27 A:92J801 2.3 28.2 1.0 C28 A:92J801 3.1 25.4 1.0 C26 A:92J801 3.2 28.8 1.0 CG2 A:ILE513 3.6 15.9 1.0 CD2 A:LEU567 3.8 20.2 1.0 CD1 A:LEU567 4.3 20.8 1.0 C23 A:92J801 4.4 23.9 1.0 CD2 A:LEU505 4.4 26.3 1.0 C25 A:92J801 4.4 30.1 1.0 CG2 A:THR508 4.6 21.1 1.0 O A:ILE592 4.7 20.5 1.0 CG A:LEU567 4.7 21.9 1.0 CG1 A:VAL504 4.9 27.4 1.0 C24 A:92J801 4.9 27.5 1.0 CB A:ILE513 5.0 18.6 1.0 CD1 A:ILE513 5.0 19.1 1.0

Fluorine binding site 3 out of 6 in the Braf in Complex with RAF709


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Braf in Complex with RAF709 within 5.0Å range: probe atom residue distance (Å) B Occ A:F801 b:30.2 occ:1.00 F31 A:92J801 0.0 30.2 1.0 C30 A:92J801 1.4 30.9 1.0 F33 A:92J801 2.2 35.8 1.0 F32 A:92J801 2.2 33.0 1.0 C27 A:92J801 2.4 28.2 1.0 C26 A:92J801 2.9 28.8 1.0 CD2 A:HIS574 3.6 25.5 1.0 C28 A:92J801 3.7 25.4 1.0 CD1 A:LEU567 3.7 20.8 1.0 CH2 A:TRP604 3.8 55.1 1.0 NE2 A:HIS574 4.1 25.1 1.0 CD2 A:LEU567 4.2 20.2 1.0 CG A:HIS574 4.2 24.8 1.0 C25 A:92J801 4.2 30.1 1.0 CZ3 A:TRP604 4.3 54.9 1.0 CG2 A:ILE572 4.4 24.9 1.0 CZ2 A:TRP604 4.5 55.0 1.0 CG A:LEU567 4.6 21.9 1.0 CG1 A:VAL504 4.7 27.4 1.0 CB A:HIS574 4.8 22.3 1.0 C23 A:92J801 4.8 23.9 1.0 CA A:HIS574 4.8 22.5 1.0 CE1 A:HIS574 4.9 25.2 1.0

Fluorine binding site 4 out of 6 in the Braf in Complex with RAF709


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Braf in Complex with RAF709 within 5.0Å range: probe atom residue distance (Å) B Occ B:F801 b:32.2 occ:1.00 F33 B:92J801 0.0 32.2 1.0 C30 B:92J801 1.4 32.7 1.0 F31 B:92J801 2.2 35.2 1.0 F32 B:92J801 2.2 35.5 1.0 C27 B:92J801 2.4 28.9 1.0 C28 B:92J801 2.8 24.2 1.0 CA B:GLY593 3.4 21.2 1.0 C B:GLY593 3.5 23.5 1.0 C26 B:92J801 3.6 31.5 1.0 O B:GLY593 3.6 23.0 1.0 CD2 B:HIS574 3.7 25.0 1.0 NE2 B:HIS574 3.7 24.9 1.0 N B:GLY593 3.8 21.7 1.0 CG2 B:ILE592 4.0 16.9 1.0 O B:ILE592 4.0 22.1 1.0 C B:ILE592 4.1 23.1 1.0 N B:ASP594 4.1 21.1 1.0 C23 B:92J801 4.2 24.3 1.0 CD1 B:LEU567 4.4 22.9 1.0 C25 B:92J801 4.7 33.0 1.0 CG B:HIS574 4.8 24.4 1.0 CE1 B:HIS574 4.8 24.6 1.0 O29 B:92J801 4.9 21.6 1.0 CB B:ASP594 4.9 23.6 1.0 C24 B:92J801 4.9 30.2 1.0 CB B:ILE592 5.0 19.5 1.0 CG2 B:ILE513 5.0 19.4 1.0

Fluorine binding site 5 out of 6 in the Braf in Complex with RAF709


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Braf in Complex with RAF709 within 5.0Å range: probe atom residue distance (Å) B Occ B:F801 b:35.5 occ:1.00 F32 B:92J801 0.0 35.5 1.0 C30 B:92J801 1.3 32.7 1.0 F33 B:92J801 2.2 32.2 1.0 F31 B:92J801 2.2 35.2 1.0 C27 B:92J801 2.3 28.9 1.0 C28 B:92J801 3.1 24.2 1.0 C26 B:92J801 3.2 31.5 1.0 CG2 B:ILE513 3.7 19.4 1.0 CD2 B:LEU567 4.1 21.9 1.0 CD2 B:LEU505 4.2 27.9 1.0 C23 B:92J801 4.3 24.3 1.0 CD1 B:LEU567 4.5 22.9 1.0 C25 B:92J801 4.5 33.0 1.0 CG2 B:THR508 4.7 22.6 1.0 O B:ILE592 4.7 22.1 1.0 CG1 B:VAL504 4.8 25.9 1.0 CA B:GLY593 4.9 21.2 1.0 C24 B:92J801 4.9 30.2 1.0 CG B:LEU567 4.9 23.3 1.0 OG1 B:THR508 5.0 22.4 1.0

Fluorine binding site 6 out of 6 in the Braf in Complex with RAF709


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Braf in Complex with RAF709 within 5.0Å range: probe atom residue distance (Å) B Occ B:F801 b:35.2 occ:1.00 F31 B:92J801 0.0 35.2 1.0 C30 B:92J801 1.4 32.7 1.0 F33 B:92J801 2.2 32.2 1.0 F32 B:92J801 2.2 35.5 1.0 C27 B:92J801 2.4 28.9 1.0 C26 B:92J801 2.8 31.5 1.0 CH2 B:TRP604 3.5 43.1 0.8 C28 B:92J801 3.6 24.2 1.0 CD1 B:LEU567 3.9 22.9 1.0 CD2 B:HIS574 4.0 25.0 1.0 CZ3 B:TRP604 4.1 42.6 0.8 C25 B:92J801 4.2 33.0 1.0 CG2 B:ILE572 4.2 24.9 1.0 CZ2 B:TRP604 4.2 43.2 0.8 CD2 B:LEU567 4.3 21.9 1.0 NE2 B:HIS574 4.4 24.9 1.0 CG1 B:VAL504 4.5 25.9 1.0 CG B:HIS574 4.6 24.4 1.0 CG B:LEU567 4.7 23.3 1.0 C23 B:92J801 4.8 24.3 1.0 C24 B:92J801 5.0 30.2 1.0

G.A.Nishiguchi, A.Rico, H.Tanner, R.J.Aversa, B.R.Taft, S.Subramanian, L.Setti, M.T.Burger, L.Wan, V.Tamez, A.Smith, Y.Lou, P.A.Barsanti, B.A.Appleton, M.Mamo, L.Tandeske, I.Dix, J.E.Tellew, S.Huang, L.A.Mathews Griner, V.G.Cooke, A.Van Abbema, H.Merritt, S.Ma, K.Gampa, F.Feng, J.Yuan, Y.Wang, J.R.Haling, S.Vaziri, M.Hekmat-Nejad, J.M.Jansen, V.Polyakov, R.Zang, V.Sethuraman, P.Amiri, M.Singh, E.Lees, W.Shao, D.D.Stuart, M.P.Dillon, S.Ramurthy. Design and Discovery of N-(2-Methyl-5'-Morpholino-6'-((Tetrahydro-2H-Pyran-4-Yl)Oxy) -[3,3'-Bipyridin]-5-Yl)-3-(Trifluoromethyl)Benzamide (RAF709): A Potent, Selective, and Efficacious Raf Inhibitor Targeting Ras Mutant Cancers. J. Med. Chem. V. 60 4869 2017.
ISSN: ISSN 1520-4804
PubMed: 28557458
DOI: 10.1021/ACS.JMEDCHEM.6B01862