Fluorine in PDB 5fto: Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib

All present enzymatic activity of Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib:
2.7.10.1;

The structure of Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib, PDB code: 5fto was solved by R.Bossi, G.Canevari, M.Fasolini, M.Menichincheri, E.Ardini, P.Magnaghi, N.Avanzi, P.Banfi, L.Buffa, L.Ceriani, M.Colombo, L.Corti, D.Donati, E.Felder, C.Fiorelli, F.Fiorentini, A.Galvani, A.Isacchi, A.Lombardi Borgia, C.Marchionni, M.Nesi, C.Orrenius, A.Panzeri, E.Perrone, E.Pesenti, L.Rusconi, M.B.Saccardo, E.Vanotti, P.Orsini, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	31.34 / 2.22
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	52.435, 58.471, 105.089, 90.00, 90.00, 90.00
R / Rfree (%)	19.605 / 25.701

The binding sites of Fluorine atom in the Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib (pdb code 5fto). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib, PDB code: 5fto:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib within 5.0Å range: probe atom residue distance (Å) B Occ A:F2402 b:20.2 occ:1.00 F36 A:YMX2402 0.0 20.2 1.0 C35 A:YMX2402 1.1 19.6 1.0 C34 A:YMX2402 2.1 19.4 1.0 C37 A:YMX2402 2.1 19.2 1.0 C33 A:YMX2402 3.3 19.2 1.0 C38 A:YMX2402 3.4 18.9 1.0 CE2 A:PHE1127 3.6 36.5 1.0 C24 A:YMX2402 3.6 29.9 1.0 CB A:ASP1203 3.6 19.4 1.0 CD2 A:PHE1127 3.6 36.4 1.0 C40 A:YMX2402 3.8 19.0 1.0 C25 A:YMX2402 3.9 30.3 1.0 O A:ARG1253 4.0 18.1 1.0 CZ A:PHE1127 4.2 36.1 1.0 F39 A:YMX2402 4.2 18.6 1.0 O26 A:YMX2402 4.3 31.5 1.0 CG A:PHE1127 4.3 36.2 1.0 CG A:ASP1203 4.4 20.6 1.0 CD2 A:LEU1256 4.4 15.3 1.0 C32 A:YMX2402 4.5 19.1 1.0 OD1 A:ASP1203 4.6 20.9 1.0 CA A:ASP1203 4.6 18.6 1.0 CE1 A:PHE1127 4.8 35.7 1.0 CD1 A:PHE1127 4.8 36.0 1.0 C23 A:YMX2402 4.9 28.9 1.0 N A:ASP1203 4.9 18.2 1.0

Fluorine binding site 2 out of 2 in the Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of the Alk Kinase Domain in Complex with Entrectinib within 5.0Å range: probe atom residue distance (Å) B Occ A:F2402 b:18.6 occ:1.00 F39 A:YMX2402 0.0 18.6 1.0 C38 A:YMX2402 1.0 18.9 1.0 C40 A:YMX2402 2.1 19.0 1.0 C37 A:YMX2402 2.1 19.2 1.0 C A:GLY1269 3.3 17.2 1.0 C35 A:YMX2402 3.4 19.6 1.0 C33 A:YMX2402 3.4 19.2 1.0 C A:ASN1254 3.4 16.8 1.0 O A:ASN1254 3.5 16.5 1.0 N A:ASP1270 3.5 17.5 1.0 O A:GLY1269 3.6 17.8 1.0 CA A:GLY1269 3.6 16.3 1.0 CA A:ASN1254 3.6 17.4 1.0 CB A:ASP1270 3.7 17.9 1.0 CG A:LEU1256 3.7 15.3 1.0 N A:CYS1255 3.8 16.1 1.0 C34 A:YMX2402 3.8 19.4 1.0 O A:ARG1253 3.9 18.1 1.0 CD1 A:LEU1256 3.9 15.7 1.0 N A:GLY1269 4.1 15.8 1.0 CA A:ASP1270 4.2 17.9 1.0 F36 A:YMX2402 4.2 20.2 1.0 CD2 A:LEU1256 4.3 15.3 1.0 C A:CYS1255 4.4 15.9 1.0 O A:CYS1255 4.4 15.7 1.0 CA A:CYS1255 4.4 15.7 1.0 C32 A:YMX2402 4.5 19.1 1.0 N A:ASN1254 4.6 17.7 1.0 CB A:ASN1254 4.6 18.1 1.0 C A:ARG1253 4.7 17.8 1.0 N A:LEU1256 4.8 15.7 1.0 OD1 A:ASN1254 4.8 19.5 1.0 O A:HOH2041 4.9 27.7 1.0 CG A:ASP1270 4.9 18.3 1.0 CB A:LEU1256 4.9 15.5 1.0 C31 A:YMX2402 5.0 18.9 1.0

M.Menichincheri, E.Ardini, P.Magnaghi, N.Avanzi, P.Banfi, R.T.Bossi, L.Buffa, G.Canevari, L.Ceriani, M.Colombo, L.Corti, D.Donati, M.Fasolini, E.R.Felder, C.Fiorelli, F.Fiorentini, A.Galvani, A.Isacchi, A.L.Borgia, C.Marchionni, M.Nesi, C.Orrenius, A.Panzeri, E.Pesenti, L.Rusconi, B.M.Saccardo, E.Vanotti, E.Perrone, P.Orsini. Discovery of Entrectinib: A New 3-Aminoindazole As A Potent Anaplastic Lymphoma Kinase (Alk), C-Ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-Trks) Inhibitor. J.Med.Chem. V. 59 3392 2016.
ISSN: ISSN 0022-2623
PubMed: 27003761
DOI: 10.1021/ACS.JMEDCHEM.6B00064