Fluorine in PDB 5to8: Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency

All present enzymatic activity of Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency:
2.7.10.2;

The structure of Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency, PDB code: 5to8 was solved by Z.E.Newby, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	43.12 / 1.98
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	37.625, 93.565, 43.214, 90.00, 93.85, 90.00
R / Rfree (%)	20.3 / 23.5

The binding sites of Fluorine atom in the Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency (pdb code 5to8). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency, PDB code: 5to8:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:23.8 occ:1.00 F37 A:7FM701 0.0 23.8 1.0 C07 A:7FM701 1.4 22.4 1.0 F38 A:7FM701 2.2 21.0 1.0 F39 A:7FM701 2.2 19.8 1.0 C05 A:7FM701 2.4 18.9 1.0 C06 A:7FM701 2.7 19.7 1.0 CB A:MET502 3.3 18.4 1.0 O A:GLU503 3.4 19.2 1.0 CB A:VAL487 3.5 17.9 1.0 C04 A:7FM701 3.7 19.2 1.0 CG1 A:VAL487 3.7 19.6 1.0 CE A:MET502 3.8 20.1 1.0 CG A:MET502 3.9 17.6 1.0 CG2 A:VAL487 3.9 18.6 1.0 N01 A:7FM701 4.1 16.3 1.0 CE1 A:TYR505 4.3 18.8 1.0 N18 A:7FM701 4.3 18.6 1.0 OD2 A:ASP567 4.5 35.0 1.0 C A:GLU503 4.6 21.8 1.0 CA A:MET502 4.6 20.6 1.0 CD1 A:TYR505 4.6 18.8 1.0 N A:GLU503 4.7 16.8 1.0 SD A:MET502 4.7 20.9 1.0 N03 A:7FM701 4.7 18.2 1.0 C A:MET502 4.8 21.2 1.0 CA A:VAL487 4.8 16.7 1.0 C02 A:7FM701 4.9 21.3 1.0 CB A:ALA455 4.9 18.4 1.0 O A:LYS488 4.9 17.7 1.0 O A:HOH844 5.0 26.5 1.0

Fluorine binding site 2 out of 3 in the Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:21.0 occ:1.00 F38 A:7FM701 0.0 21.0 1.0 C07 A:7FM701 1.3 22.4 1.0 F37 A:7FM701 2.2 23.8 1.0 F39 A:7FM701 2.2 19.8 1.0 C05 A:7FM701 2.4 18.9 1.0 C04 A:7FM701 3.0 19.2 1.0 N18 A:7FM701 3.1 18.6 1.0 CB A:MET502 3.4 18.4 1.0 C06 A:7FM701 3.4 19.7 1.0 CG A:MET502 3.5 17.6 1.0 O A:HOH844 3.5 26.5 1.0 CB A:ALA455 3.8 18.4 1.0 OD2 A:ASP567 4.0 35.0 1.0 N03 A:7FM701 4.3 18.2 1.0 C19 A:7FM701 4.4 21.4 1.0 CE A:MET502 4.5 20.1 1.0 N01 A:7FM701 4.6 16.3 1.0 CD A:LYS457 4.7 32.1 1.0 O A:GLU503 4.7 19.2 1.0 CG A:LYS457 4.7 23.9 1.0 NZ A:LYS457 4.8 37.5 1.0 CG A:ASP567 4.8 33.1 1.0 SD A:MET502 4.8 20.9 1.0 CA A:MET502 4.9 20.6 1.0 O A:ALA455 4.9 19.1 1.0 C02 A:7FM701 4.9 21.3 1.0 OD1 A:ASP567 5.0 39.2 1.0

Fluorine binding site 3 out of 3 in the Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:19.8 occ:1.00 F39 A:7FM701 0.0 19.8 1.0 C07 A:7FM701 1.4 22.4 1.0 F38 A:7FM701 2.2 21.0 1.0 F37 A:7FM701 2.2 23.8 1.0 C05 A:7FM701 2.3 18.9 1.0 C04 A:7FM701 2.9 19.2 1.0 N18 A:7FM701 3.0 18.6 1.0 OD2 A:ASP567 3.1 35.0 1.0 O A:HOH844 3.2 26.5 1.0 C06 A:7FM701 3.4 19.7 1.0 O A:HOH862 3.9 25.3 1.0 CG1 A:VAL487 3.9 19.6 1.0 CG2 A:VAL487 4.1 18.6 1.0 CD2 A:LEU556 4.1 14.1 1.0 N03 A:7FM701 4.1 18.2 1.0 CB A:VAL487 4.2 17.9 1.0 CG A:ASP567 4.2 33.1 1.0 C25 A:7FM701 4.3 19.6 1.0 C19 A:7FM701 4.4 21.4 1.0 N01 A:7FM701 4.5 16.3 1.0 N A:ASP567 4.6 24.1 1.0 CG A:LEU556 4.7 16.1 1.0 C02 A:7FM701 4.8 21.3 1.0 CE A:MET502 4.8 20.1 1.0 C20 A:7FM701 4.8 19.1 1.0 CA A:GLY566 4.9 21.5 1.0 OD1 A:ASP567 4.9 39.2 1.0 CB A:MET502 4.9 18.4 1.0

J.Farand, N.Mai, J.Chandrasekhar, Z.E.Newby, J.Van Veldhuizen, J.Loyer-Drew, C.Venkataramani, J.Guerrero, A.Kwok, N.Li, Y.Zherebina, S.Wilbert, J.Zablocki, G.Phillips, W.J.Watkins, R.Mourey, G.T.Notte. Selectivity Switch Between Fak and PYK2: Macrocyclization of Fak Inhibitors Improves PYK2 Potency. Bioorg. Med. Chem. Lett. V. 26 5926 2016.
ISSN: ESSN 1464-3405
PubMed: 27876318
DOI: 10.1016/J.BMCL.2016.10.092