Fluorine in PDB 6thw: IRAK4 in Complex with Inhibitor

All present enzymatic activity of IRAK4 in Complex with Inhibitor:
2.7.11.1;

The structure of IRAK4 in Complex with Inhibitor, PDB code: 6thw was solved by Y.Xue, A.Aagaard, S.L.Degorce, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	44.41 / 2.44
Space group	I 2 2 2
Cell size a, b, c (Å), α, β, γ (°)	87.470, 110.540, 142.830, 90.00, 90.00, 90.00
R / Rfree (%)	24.1 / 27.1

The binding sites of Fluorine atom in the IRAK4 in Complex with Inhibitor (pdb code 6thw). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the IRAK4 in Complex with Inhibitor, PDB code: 6thw:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the IRAK4 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of IRAK4 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F501 b:57.5 occ:1.00 F36 A:NBK501 0.0 57.5 1.0 C10 A:NBK501 1.3 52.4 1.0 C1 A:NBK501 2.3 50.9 1.0 C11 A:NBK501 2.4 50.5 1.0 CB A:TYR262 2.8 72.0 1.0 C2 A:NBK501 2.9 55.0 1.0 C6 A:NBK501 2.9 55.0 1.0 CG A:TYR262 3.1 70.6 1.0 N29 A:NBK501 3.6 52.3 1.0 C7 A:NBK501 3.6 49.2 1.0 CD2 A:TYR262 3.6 71.8 1.0 CD1 A:TYR262 3.6 69.8 1.0 O A:VAL263 3.7 76.2 1.0 CD1 A:LEU318 3.9 59.9 1.0 C8 A:NBK501 4.0 51.7 1.0 N26 A:NBK501 4.1 51.2 1.0 C3 A:NBK501 4.2 55.1 1.0 CA A:TYR262 4.2 75.9 1.0 CG1 A:VAL246 4.3 76.6 1.0 CB A:VAL246 4.3 79.2 1.0 CB A:ALA211 4.5 75.1 1.0 CE2 A:TYR262 4.5 71.9 1.0 CE1 A:TYR262 4.5 67.3 1.0 C A:TYR262 4.6 80.8 1.0 CG2 A:VAL246 4.6 79.3 1.0 N30 A:NBK501 4.7 50.9 1.0 CG A:MET265 4.7 70.7 1.0 N A:VAL263 4.8 78.5 1.0 C A:VAL263 4.8 79.2 1.0 CZ A:TYR262 4.9 75.8 1.0 C13 A:NBK501 5.0 52.1 1.0

Fluorine binding site 2 out of 2 in the IRAK4 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of IRAK4 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:F501 b:49.8 occ:1.00 F36 B:NBK501 0.0 49.8 1.0 C10 B:NBK501 1.3 44.2 1.0 C1 B:NBK501 2.3 44.8 1.0 C11 B:NBK501 2.4 44.4 1.0 CB B:TYR262 2.9 47.5 1.0 C6 B:NBK501 3.0 48.5 1.0 C2 B:NBK501 3.1 50.0 1.0 CG B:TYR262 3.1 48.8 1.0 O B:VAL263 3.5 54.2 1.0 C7 B:NBK501 3.5 45.0 1.0 N29 B:NBK501 3.6 45.8 1.0 CD1 B:TYR262 3.7 50.3 1.0 CD2 B:TYR262 3.7 50.0 1.0 CD1 B:LEU318 3.9 50.6 1.0 C8 B:NBK501 4.0 43.7 1.0 CB B:ALA211 4.2 47.2 1.0 CG1 B:VAL246 4.2 47.6 1.0 CB B:VAL246 4.2 49.6 1.0 N26 B:NBK501 4.2 47.3 1.0 C3 B:NBK501 4.3 51.7 1.0 CA B:TYR262 4.4 47.8 1.0 CG2 B:VAL246 4.5 50.0 1.0 CE1 B:TYR262 4.6 50.5 1.0 N30 B:NBK501 4.6 43.4 1.0 C B:VAL263 4.6 54.8 1.0 C B:TYR262 4.6 53.0 1.0 N B:VAL263 4.7 50.7 1.0 CE2 B:TYR262 4.7 51.3 1.0 CG B:MET265 4.7 54.9 1.0

S.L.Degorce, A.Aagaard, R.Anjum, I.A.Cumming, C.R.Diene, C.Fallan, T.Johnson, K.J.Leuchowius, A.L.Orton, S.Pearson, G.R.Robb, A.Rosen, G.B.Scarfe, J.S.Scott, J.M.Smith, O.R.Steward, I.Terstiege, M.J.Tucker, P.Turner, S.D.Wilkinson, G.L.Wrigley, Y.Xue. Improving Metabolic Stability and Removing Aldehyde Oxidase Liability in A 5-Azaquinazoline Series of IRAK4 Inhibitors. Bioorg.Med.Chem. V. 28 15815 2020.
ISSN: ESSN 1464-3391
PubMed: 33091850
DOI: 10.1016/J.BMC.2020.115815