Fluorine in PDB 8e9f: Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10)

The structure of Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10), PDB code: 8e9f was solved by T.A.Rietz, S.W.Fesik, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	29.56 / 1.55
Space group	P 21 21 2
Cell size a, b, c (Å), α, β, γ (°)	81.361, 86.04, 41.032, 90, 90, 90
R / Rfree (%)	15.9 / 18.4

The binding sites of Fluorine atom in the Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10) (pdb code 8e9f). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10), PDB code: 8e9f:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10) within 5.0Å range: probe atom residue distance (Å) B Occ A:F402 b:24.7 occ:1.00 F1 A:UY9402 0.0 24.7 1.0 C17 A:UY9402 1.3 22.4 1.0 F2 A:UY9402 2.1 26.3 1.0 F3 A:UY9402 2.2 21.3 1.0 C12 A:UY9402 2.3 14.3 1.0 N3 A:UY9402 3.1 16.9 1.0 C10 A:UY9402 3.3 13.9 1.0 CD2 A:LEU321 3.4 15.5 1.0 O A:VAL48 3.4 17.2 1.0 CB A:ALA47 3.5 14.8 1.0 CA A:SER49 3.6 12.8 1.0 CB A:SER49 3.7 13.2 1.0 C1 A:UY9402 3.7 15.5 1.0 C A:VAL48 3.7 14.0 1.0 N A:SER49 3.9 11.4 1.0 C6 A:UY9402 4.0 13.6 1.0 N4 A:UY9402 4.2 18.4 1.0 C A:ALA47 4.2 15.4 1.0 O A:ALA47 4.3 15.6 1.0 C13 A:UY9402 4.3 15.8 1.0 N A:VAL48 4.5 13.2 1.0 CA A:ALA47 4.5 15.8 1.0 C2 A:UY9402 4.6 13.6 1.0 CA A:VAL48 4.7 13.5 1.0 CG A:LEU321 4.9 17.4 1.0 OG A:SER49 4.9 13.6 1.0 C A:SER49 4.9 12.9 1.0 CG2 A:ILE305 4.9 13.7 1.0 C5 A:UY9402 5.0 12.4 1.0

Fluorine binding site 2 out of 3 in the Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10) within 5.0Å range: probe atom residue distance (Å) B Occ A:F402 b:26.3 occ:1.00 F2 A:UY9402 0.0 26.3 1.0 C17 A:UY9402 1.3 22.4 1.0 F3 A:UY9402 2.1 21.3 1.0 F1 A:UY9402 2.1 24.7 1.0 C12 A:UY9402 2.3 14.3 1.0 C10 A:UY9402 3.0 13.9 1.0 C1 A:UY9402 3.0 15.5 1.0 C2 A:UY9402 3.3 13.6 1.0 CD2 A:LEU321 3.3 15.5 1.0 C7 A:UY9402 3.4 15.4 1.0 N3 A:UY9402 3.5 16.9 1.0 C6 A:UY9402 3.8 13.6 1.0 O A:HOH826 4.1 50.6 1.0 C3 A:UY9402 4.2 12.8 1.0 C13 A:UY9402 4.2 15.8 1.0 O A:HOH809 4.2 42.0 1.0 O A:HOH736 4.3 37.9 1.0 N4 A:UY9402 4.4 18.4 1.0 CG A:LEU321 4.6 17.4 1.0 CB A:ALA47 4.6 14.8 1.0 C5 A:UY9402 4.6 12.4 1.0 O A:HOH735 4.6 21.6 1.0 CD1 A:LEU321 4.6 16.4 1.0 C4 A:UY9402 4.7 12.3 1.0 C8 A:UY9402 4.8 19.1 1.0 CD1 A:ILE305 5.0 17.1 1.0 CE1 A:TYR260 5.0 17.9 1.0

Fluorine binding site 3 out of 3 in the Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Wd Repeat-Containing Protein 5 Complexed with 4-(7-((1H-Imidazol-1- Yl)Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-1-Oxo-3, 4-Dihydroisoquinolin-2(1H)-Yl)-6-Ethyl-N-Methylquinoline-8- Carboxamide (Compound 10) within 5.0Å range: probe atom residue distance (Å) B Occ A:F402 b:21.3 occ:1.00 F3 A:UY9402 0.0 21.3 1.0 C17 A:UY9402 1.3 22.4 1.0 F2 A:UY9402 2.1 26.3 1.0 F1 A:UY9402 2.2 24.7 1.0 C12 A:UY9402 2.3 14.3 1.0 N3 A:UY9402 2.6 16.9 1.0 CB A:ALA47 3.3 14.8 1.0 O A:HOH693 3.5 37.6 1.0 C10 A:UY9402 3.6 13.9 1.0 O A:HOH826 3.8 50.6 1.0 N4 A:UY9402 3.9 18.4 1.0 CB A:ALA65 4.1 17.1 1.0 CD2 A:LEU321 4.2 15.5 1.0 O A:HOH735 4.2 21.6 1.0 C13 A:UY9402 4.4 15.8 1.0 C1 A:UY9402 4.4 15.5 1.0 CA A:ALA47 4.6 15.8 1.0 O A:HOH736 4.6 37.9 1.0 C7 A:UY9402 4.7 15.4 1.0 O A:ALA47 4.8 15.6 1.0 C A:ALA47 4.8 15.4 1.0 O A:HOH809 4.9 42.0 1.0 C2 A:UY9402 4.9 13.6 1.0

K.B.Teuscher, S.Chowdhury, K.M.Meyers, J.Tian, J.Sai, M.Van Meveren, T.M.South, J.L.Sensintaffar, T.A.Rietz, S.Goswami, J.Wang, B.C.Grieb, S.L.Lorey, G.C.Howard, Q.Liu, W.J.Moore, G.M.Stott, W.P.Tansey, T.Lee, S.W.Fesik. Structure-Based Discovery of Potent Wd Repeat Domain 5 Inhibitors That Demonstrate Efficacy and Safety in Preclinical Animal Models. Proc.Natl.Acad.Sci.Usa V. 120 97120 2023.
ISSN: ESSN 1091-6490
PubMed: 36574664
DOI: 10.1073/PNAS.2211297120