Fluorine in PDB 6qxu: Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One

All present enzymatic activity of Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One:
2.4.2.30;

The structure of Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One, PDB code: 6qxu was solved by D.Musil, D.Lehmann, H.-P.Buchstaller, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	13.79 / 1.20
Space group	C 2 2 21
Cell size a, b, c (Å), α, β, γ (°)	77.940, 94.640, 62.340, 90.00, 90.00, 90.00
R / Rfree (%)	18.9 / 21.3

The structure of Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One also contains other interesting chemical elements:

Zinc

(Zn)

1 atom

The binding sites of Fluorine atom in the Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One (pdb code 6qxu). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One, PDB code: 6qxu:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One within 5.0Å range: probe atom residue distance (Å) B Occ A:F1402 b:14.8 occ:1.00 F20 A:JKN1402 0.0 14.8 1.0 C1 A:JKN1402 1.3 12.6 1.0 C3 A:JKN1402 2.3 12.6 1.0 C2 A:JKN1402 2.3 12.9 1.0 N5 A:JKN1402 2.7 13.2 1.0 OH A:TYR1224 3.3 18.9 1.0 CZ A:TYR1224 3.4 15.9 1.0 O A:HOH1540 3.4 20.2 1.0 CE2 A:TYR1203 3.5 16.8 1.0 CD2 A:TYR1213 3.6 14.2 1.0 C6 A:JKN1402 3.6 12.9 1.0 C4 A:JKN1402 3.6 13.2 1.0 CG A:TYR1213 3.6 13.2 1.0 CD2 A:TYR1203 3.6 15.7 1.0 CB A:TYR1213 3.7 13.0 1.0 CE1 A:TYR1224 3.9 16.7 1.0 CE2 A:TYR1224 4.0 15.3 1.0 C11 A:JKN1402 4.0 12.7 1.0 C7 A:JKN1402 4.1 12.7 1.0 O A:HOH1501 4.2 28.9 1.0 OE1 A:GLU1291 4.2 21.0 1.0 CE2 A:TYR1213 4.3 13.5 1.0 CD1 A:TYR1213 4.4 13.7 1.0 O A:HOH1505 4.6 24.9 1.0 CD A:GLU1291 4.7 24.2 1.0 CD1 A:TYR1224 4.7 15.6 1.0 F21 A:JKN1402 4.7 14.8 1.0 OE2 A:GLU1291 4.7 21.7 1.0 C13 A:JKN1402 4.7 14.9 1.0 CZ A:TYR1203 4.7 18.2 1.0 CD2 A:TYR1224 4.7 14.9 1.0 C8 A:JKN1402 4.8 13.7 1.0 O A:HOH1512 4.8 33.6 1.0 N9 A:JKN1402 4.9 13.4 1.0 C12 A:JKN1402 4.9 12.9 1.0 CG A:TYR1203 5.0 15.0 1.0

Fluorine binding site 2 out of 2 in the Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Human TNKS1 in Complex with 6,8-Difluoro-2-[4-(1-Hydroxy-1-Methyl- Ethyl)-Phenyl]-3H-Quinazolin-4-One within 5.0Å range: probe atom residue distance (Å) B Occ A:F1402 b:14.8 occ:1.00 F21 A:JKN1402 0.0 14.8 1.0 C6 A:JKN1402 1.3 12.9 1.0 C3 A:JKN1402 2.4 12.6 1.0 C7 A:JKN1402 2.4 12.7 1.0 CE A:LYS1220 3.2 17.2 1.0 O A:PHE1214 3.3 13.6 1.0 CD A:LYS1220 3.3 17.4 1.0 CB A:GLU1291 3.4 19.6 1.0 CB A:ALA1215 3.4 14.7 1.0 C A:PHE1214 3.6 13.2 1.0 CG A:LYS1220 3.6 16.7 1.0 C1 A:JKN1402 3.6 12.6 1.0 CA A:ALA1215 3.6 13.1 1.0 C4 A:JKN1402 3.6 13.2 1.0 N A:ALA1215 3.8 13.0 1.0 NZ A:LYS1220 3.8 19.6 1.0 O A:ALA1290 4.0 18.3 1.0 CA A:GLU1291 4.1 18.2 1.0 C2 A:JKN1402 4.1 12.9 1.0 OE2 A:GLU1291 4.3 21.7 1.0 CD A:GLU1291 4.5 24.2 1.0 CA A:PHE1214 4.5 11.7 1.0 CB A:LYS1220 4.6 14.6 1.0 CG A:GLU1291 4.6 19.9 1.0 N A:PHE1214 4.6 12.3 1.0 F20 A:JKN1402 4.7 14.8 1.0 O A:HOH1537 4.8 16.4 1.0 C8 A:JKN1402 4.9 13.7 1.0 C A:ALA1290 4.9 18.6 1.0 N A:GLU1291 4.9 16.9 1.0 O A:HOH1501 5.0 28.9 1.0

H.P.Buchstaller, U.Anlauf, D.Dorsch, D.Kuhn, M.Lehmann, B.Leuthner, D.Musil, D.Radtki, C.Ritzert, F.Rohdich, R.Schneider, C.Esdar. Discovery and Optimization of 2-Arylquinazolin-4-Ones Into A Potent and Selective Tankyrase Inhibitor Modulating Wnt Pathway Activity. J.Med.Chem. V. 62 7897 2019.
ISSN: ISSN 0022-2623
PubMed: 31381853
DOI: 10.1021/ACS.JMEDCHEM.9B00656