Fluorine in PDB 7nti: Structure of TAK1 in Complex with Compound 22

All present enzymatic activity of Structure of TAK1 in Complex with Compound 22:
2.7.11.25;

The structure of Structure of TAK1 in Complex with Compound 22, PDB code: 7nti was solved by J.J.N.Veerman, Y.B.Bruseker, E.Damen, E.H.Heijne, W.Van Bruggen, K.F.W.Hekking, R.Winkel, C.D.Hupp, A.D.Keefe, J.Liu, H.A.Thomson, Y.Zhang, J.W.Cuozzo, A.J.Mcriner, M.J.Mulvihill, P.Van Rijnsbergen, B.Zech, L.M.Renzetti, L.Babiss, G.Mueller, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	28.60 / 1.98
Space group	I 2 2 2
Cell size a, b, c (Å), α, β, γ (°)	58.165, 134.542, 152.693, 90, 90, 90
R / Rfree (%)	22.1 / 24.9

The binding sites of Fluorine atom in the Structure of TAK1 in Complex with Compound 22 (pdb code 7nti). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Structure of TAK1 in Complex with Compound 22, PDB code: 7nti:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Structure of TAK1 in Complex with Compound 22


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Structure of TAK1 in Complex with Compound 22 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1008 b:69.6 occ:0.50 F1 A:UWZ1008 0.0 69.6 0.5 F1 A:UWZ1008 0.1 52.2 0.5 C16 A:UWZ1008 1.4 64.4 0.5 C16 A:UWZ1008 1.4 50.5 0.5 F A:UWZ1008 2.2 56.5 0.5 F A:UWZ1008 2.2 69.3 0.5 O2 A:UWZ1008 2.2 67.7 0.5 O2 A:UWZ1008 2.3 54.7 0.5 C11 A:UWZ1008 2.7 67.8 0.5 C11 A:UWZ1008 2.8 56.2 0.5 C12 A:UWZ1008 2.8 66.5 0.5 C12 A:UWZ1008 2.8 55.0 0.5 CB A:CYS174 3.2 64.6 1.0 SG A:CYS174 3.3 82.1 1.0 C A:ASN161 3.8 43.0 1.0 O A:ASN161 3.9 39.4 1.0 OD2 A:ASP175 3.9 102.0 1.0 CA A:ASN161 4.0 40.5 1.0 CB A:LEU163 4.0 34.9 1.0 O A:PRO160 4.1 35.4 1.0 C10 A:UWZ1008 4.1 65.6 0.5 C10 A:UWZ1008 4.1 54.6 0.5 C13 A:UWZ1008 4.1 63.3 0.5 C13 A:UWZ1008 4.2 53.2 0.5 N A:LEU163 4.2 36.5 1.0 N A:LEU162 4.2 40.6 1.0 C A:LEU162 4.4 37.4 1.0 CA A:LEU163 4.4 37.7 1.0 CA A:CYS174 4.6 65.0 1.0 CD1 A:LEU163 4.6 41.8 1.0 CA A:LEU162 4.7 38.8 1.0 C15 A:UWZ1008 4.8 57.7 0.5 C15 A:UWZ1008 4.8 48.3 0.5 N A:CYS174 4.8 53.2 1.0 C A:PRO160 4.8 34.8 1.0 O A:LEU162 4.9 33.5 1.0 CG A:LEU163 4.9 40.9 1.0 N A:ASN161 4.9 35.6 1.0 CG A:ASP175 4.9 95.8 1.0 C5 A:UWZ1008 5.0 41.7 0.5 C5 A:UWZ1008 5.0 44.1 0.5 C6 A:UWZ1008 5.0 39.8 0.5 C6 A:UWZ1008 5.0 42.0 0.5

Fluorine binding site 2 out of 4 in the Structure of TAK1 in Complex with Compound 22


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Structure of TAK1 in Complex with Compound 22 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1008 b:52.2 occ:0.50 F1 A:UWZ1008 0.0 52.2 0.5 F1 A:UWZ1008 0.1 69.6 0.5 C16 A:UWZ1008 1.3 64.4 0.5 C16 A:UWZ1008 1.4 50.5 0.5 O2 A:UWZ1008 2.2 67.7 0.5 O2 A:UWZ1008 2.2 54.7 0.5 F A:UWZ1008 2.2 56.5 0.5 F A:UWZ1008 2.2 69.3 0.5 C11 A:UWZ1008 2.7 67.8 0.5 C12 A:UWZ1008 2.7 66.5 0.5 C11 A:UWZ1008 2.7 56.2 0.5 C12 A:UWZ1008 2.8 55.0 0.5 CB A:CYS174 3.3 64.6 1.0 SG A:CYS174 3.3 82.1 1.0 C A:ASN161 3.9 43.0 1.0 O A:ASN161 3.9 39.4 1.0 CB A:LEU163 4.0 34.9 1.0 OD2 A:ASP175 4.0 102.0 1.0 C10 A:UWZ1008 4.0 65.6 0.5 C13 A:UWZ1008 4.1 63.3 0.5 C10 A:UWZ1008 4.1 54.6 0.5 C13 A:UWZ1008 4.1 53.2 0.5 O A:PRO160 4.1 35.4 1.0 CA A:ASN161 4.1 40.5 1.0 N A:LEU163 4.2 36.5 1.0 N A:LEU162 4.3 40.6 1.0 CA A:LEU163 4.4 37.7 1.0 C A:LEU162 4.4 37.4 1.0 CD1 A:LEU163 4.5 41.8 1.0 CA A:CYS174 4.6 65.0 1.0 C15 A:UWZ1008 4.7 57.7 0.5 C15 A:UWZ1008 4.7 48.3 0.5 CA A:LEU162 4.7 38.8 1.0 CG A:LEU163 4.8 40.9 1.0 O A:LEU162 4.9 33.5 1.0 N A:CYS174 4.9 53.2 1.0 C5 A:UWZ1008 4.9 41.7 0.5 C5 A:UWZ1008 4.9 44.1 0.5 C A:PRO160 4.9 34.8 1.0 C6 A:UWZ1008 4.9 39.8 0.5 C6 A:UWZ1008 4.9 42.0 0.5 N A:ASN161 5.0 35.6 1.0 CG A:ASP175 5.0 95.8 1.0

Fluorine binding site 3 out of 4 in the Structure of TAK1 in Complex with Compound 22


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Structure of TAK1 in Complex with Compound 22 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1008 b:69.3 occ:0.50 F A:UWZ1008 0.0 69.3 0.5 F A:UWZ1008 0.0 56.5 0.5 C16 A:UWZ1008 1.3 64.4 0.5 C16 A:UWZ1008 1.4 50.5 0.5 O A:PRO160 2.2 35.4 1.0 F1 A:UWZ1008 2.2 69.6 0.5 O2 A:UWZ1008 2.2 67.7 0.5 F1 A:UWZ1008 2.2 52.2 0.5 O2 A:UWZ1008 2.3 54.7 0.5 C12 A:UWZ1008 2.9 66.5 0.5 C12 A:UWZ1008 3.0 55.0 0.5 C A:PRO160 3.1 34.8 1.0 C11 A:UWZ1008 3.2 67.8 0.5 C11 A:UWZ1008 3.2 56.2 0.5 CA A:ASN161 3.4 40.5 1.0 N A:ASN161 3.6 35.6 1.0 O A:HOH1169 3.6 70.9 1.0 C A:ASN161 3.6 43.0 1.0 N A:LEU162 3.6 40.6 1.0 CB A:SER111 3.7 37.2 1.0 O A:LEU162 4.0 33.5 1.0 C13 A:UWZ1008 4.1 63.3 0.5 C13 A:UWZ1008 4.1 53.2 0.5 C A:LEU162 4.1 37.4 1.0 CA A:PRO160 4.2 29.0 1.0 CA A:SER111 4.2 40.7 1.0 O A:ASN161 4.4 39.4 1.0 OD2 A:ASP175 4.4 102.0 1.0 N A:LEU163 4.4 36.5 1.0 O A:PRO159 4.5 32.9 1.0 C10 A:UWZ1008 4.5 65.6 0.5 C15 A:UWZ1008 4.5 57.7 0.5 CA A:LEU162 4.5 38.8 1.0 C10 A:UWZ1008 4.5 54.6 0.5 C15 A:UWZ1008 4.5 48.3 0.5 CA A:LEU163 4.7 37.7 1.0 CB A:ASN161 4.8 45.4 1.0 OD1 A:ASN161 4.8 54.9 1.0 OG A:SER111 4.9 47.6 1.0

Fluorine binding site 4 out of 4 in the Structure of TAK1 in Complex with Compound 22


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Structure of TAK1 in Complex with Compound 22 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1008 b:56.5 occ:0.50 F A:UWZ1008 0.0 56.5 0.5 F A:UWZ1008 0.0 69.3 0.5 C16 A:UWZ1008 1.3 64.4 0.5 C16 A:UWZ1008 1.3 50.5 0.5 O A:PRO160 2.2 35.4 1.0 O2 A:UWZ1008 2.2 67.7 0.5 F1 A:UWZ1008 2.2 69.6 0.5 O2 A:UWZ1008 2.2 54.7 0.5 F1 A:UWZ1008 2.2 52.2 0.5 C12 A:UWZ1008 2.9 66.5 0.5 C12 A:UWZ1008 2.9 55.0 0.5 C A:PRO160 3.1 34.8 1.0 C11 A:UWZ1008 3.2 67.8 0.5 C11 A:UWZ1008 3.2 56.2 0.5 CA A:ASN161 3.4 40.5 1.0 O A:HOH1169 3.6 70.9 1.0 N A:ASN161 3.6 35.6 1.0 C A:ASN161 3.6 43.0 1.0 N A:LEU162 3.6 40.6 1.0 CB A:SER111 3.7 37.2 1.0 O A:LEU162 4.0 33.5 1.0 C13 A:UWZ1008 4.0 63.3 0.5 C13 A:UWZ1008 4.1 53.2 0.5 C A:LEU162 4.1 37.4 1.0 CA A:SER111 4.2 40.7 1.0 CA A:PRO160 4.2 29.0 1.0 O A:ASN161 4.4 39.4 1.0 N A:LEU163 4.4 36.5 1.0 OD2 A:ASP175 4.4 102.0 1.0 C15 A:UWZ1008 4.5 57.7 0.5 C10 A:UWZ1008 4.5 65.6 0.5 C10 A:UWZ1008 4.5 54.6 0.5 O A:PRO159 4.5 32.9 1.0 C15 A:UWZ1008 4.5 48.3 0.5 CA A:LEU162 4.5 38.8 1.0 CA A:LEU163 4.7 37.7 1.0 CB A:ASN161 4.8 45.4 1.0 OD1 A:ASN161 4.8 54.9 1.0 OG A:SER111 5.0 47.6 1.0 CB A:LEU163 5.0 34.9 1.0 N A:SER111 5.0 42.9 1.0

J.J.N.Veerman, Y.B.Bruseker, E.Damen, E.H.Heijne, K.F.W.Hekking, R.Winkel, C.D.Hupp, A.D.Keefe, J.Liu, H.A.Thomson, Y.Zhang, J.W.Cuozzo, A.J.Mcriner, M.J.Mulvihill, B.Zech, L.M.Renzetti, L.Babiss, G.Muller. Discovery of 2,4-1H-Imidazole Carboxamides As Potent and Selective TAK1 Inhibitors Acs Med.Chem.Lett. 2021.
ISSN: ISSN 1948-5875
DOI: 10.1021/ACSMEDCHEMLETT.0C00547