Chlorine in PDB 8udu: The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17

All present enzymatic activity of The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17:
2.7.10.1;

The structure of The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17, PDB code: 8udu was solved by J.S.Tyhonas, L.D.Arnold, J.Cox, A.Franovic, E.Gardiner, K.Grandinetti, R.Kania, T.Kanouni, M.Lardy, C.Li, E.S.Martin, N.Miller, A.Mohan, E.A.Murphy, M.Perez, L.Soroceanu, N.Timple, S.Uryu, S.Womble, S.W.Kaldor, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	34.14 / 1.74
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	55.7, 69.314, 78.473, 90, 90.96, 90
R / Rfree (%)	23 / 25.6

The binding sites of Chlorine atom in the The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17 (pdb code 8udu). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 4 binding sites of Chlorine where determined in the The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17, PDB code: 8udu:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine binding site 1 out of 4 in the The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl1001 b:38.2 occ:1.00 H A:PHE741 2.2 28.9 0.0 HD2 A:PHE741 2.9 30.2 0.0 O A:HOH1277 2.9 51.5 1.0 O A:HOH1217 2.9 46.1 1.0 HB A:THR740 3.0 31.5 0.0 O A:HOH1219 3.1 30.2 1.0 N A:PHE741 3.2 28.6 1.0 HA A:THR740 3.3 30.3 0.0 HB2 A:PHE741 3.3 29.2 0.0 HB3 A:HIS673 3.3 32.6 0.0 HB1 A:ALA609 3.3 35.5 0.0 CD2 A:PHE741 3.7 30.0 1.0 HB2 A:ALA609 3.8 35.4 0.0 CB A:THR740 3.9 31.1 1.0 CA A:THR740 3.9 30.0 1.0 CB A:ALA609 3.9 34.9 1.0 HB3 A:ALA609 3.9 35.5 0.0 HG22 A:THR740 4.0 33.4 0.0 C A:THR740 4.0 29.5 1.0 CB A:PHE741 4.1 28.9 1.0 H A:LYS742 4.2 30.6 0.0 HB2 A:HIS673 4.2 32.7 0.0 CB A:HIS673 4.2 32.3 1.0 CA A:PHE741 4.2 29.5 1.0 CG A:PHE741 4.3 28.9 1.0 HG23 A:VAL677 4.4 29.6 0.0 HG21 A:VAL677 4.4 29.7 0.0 CG2 A:THR740 4.5 33.0 1.0 O A:HOH1280 4.5 54.8 1.0 CE2 A:PHE741 4.7 29.9 1.0 HE2 A:PHE741 4.8 30.0 0.0 CG2 A:VAL677 4.8 29.6 1.0 O A:HOH1267 4.8 41.1 1.0 HG21 A:THR740 4.9 33.5 0.0 CG A:HIS673 4.9 33.7 1.0 O A:HOH1250 4.9 52.5 1.0 HG22 A:VAL677 4.9 29.6 0.0 O A:HOH1178 5.0 35.4 1.0 O A:HOH1146 5.0 34.0 1.0 HE21 A:GLN674 5.0 46.8 0.0 N A:LYS742 5.0 30.2 1.0 HA A:PHE741 5.0 29.6 0.0

Chlorine binding site 2 out of 4 in the The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl1002 b:50.1 occ:1.00 CL1 A:WIQ1002 0.0 50.1 1.0 C15 A:WIQ1002 1.7 50.8 1.0 C14 A:WIQ1002 2.7 51.3 1.0 HG13 A:VAL486 2.7 53.4 0.0 C6 A:WIQ1002 2.7 50.7 1.0 HB2 A:LYS508 2.9 51.9 0.0 C5 A:WIQ1002 3.1 50.4 1.0 HG22 A:VAL486 3.1 53.5 0.0 HG21 A:VAL555 3.1 41.5 0.0 HG21 A:VAL486 3.1 53.1 0.0 HG11 A:VAL486 3.2 53.0 0.0 CG1 A:VAL486 3.4 51.0 1.0 HG22 A:VAL555 3.4 41.9 0.0 CG2 A:VAL486 3.5 51.2 1.0 CG2 A:VAL555 3.7 39.4 1.0 HB1 A:ALA506 3.8 43.8 0.0 HD2 A:LYS508 3.8 57.9 0.0 C4 A:WIQ1002 3.9 50.3 1.0 C13 A:WIQ1002 4.0 51.9 1.0 C7 A:WIQ1002 4.0 51.3 1.0 CB A:LYS508 4.0 49.0 1.0 CB A:VAL486 4.1 50.5 1.0 HB3 A:ALA506 4.1 43.8 0.0 HG23 A:VAL555 4.3 41.6 0.0 HB3 A:PHE483 4.3 60.4 0.0 HG12 A:VAL486 4.3 53.3 0.0 CB A:ALA506 4.5 41.5 1.0 HG11 A:VAL555 4.5 41.9 0.0 HG23 A:VAL486 4.5 53.3 0.0 C8 A:WIQ1002 4.5 52.0 1.0 N A:LYS508 4.5 45.8 1.0 HA A:LYS508 4.6 51.4 0.0 HB3 A:LYS508 4.6 52.3 0.0 N1 A:WIQ1002 4.6 47.0 1.0 CA A:LYS508 4.6 48.2 1.0 HA A:VAL486 4.7 52.3 0.0 HG13 A:VAL555 4.7 42.3 0.0 HG3 A:LYS508 4.7 54.9 0.0 CD A:LYS508 4.7 55.4 1.0 C A:VAL507 4.7 45.0 1.0 CG A:LYS508 4.7 52.0 1.0 H A:LYS508 4.8 49.3 0.0 O A:PHE483 4.8 58.5 1.0 O A:VAL507 4.9 45.2 1.0 HB A:VAL486 4.9 52.6 0.0 C3 A:WIQ1002 4.9 50.9 1.0 HB2 A:PHE483 4.9 60.3 0.0 C A:ALA506 4.9 42.0 1.0 CG1 A:VAL555 4.9 39.5 1.0 CB A:VAL555 5.0 39.0 1.0 O A:ALA506 5.0 42.1 1.0

Chlorine binding site 3 out of 4 in the The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl1001 b:52.5 occ:1.00 H B:PHE741 2.1 36.0 0.0 HD2 B:PHE741 2.8 32.7 0.0 HB3 B:HIS673 3.1 38.1 0.0 HB B:THR740 3.1 41.5 0.0 N B:PHE741 3.1 33.6 1.0 HA B:THR740 3.2 38.4 0.0 O B:HOH1185 3.2 35.0 1.0 HB2 B:PHE741 3.2 35.1 0.0 HB1 B:ALA609 3.5 39.3 0.0 OE1 B:GLN674 3.6 50.8 1.0 CD2 B:PHE741 3.6 31.5 1.0 CA B:THR740 3.8 35.6 1.0 HB2 B:ALA609 3.8 38.5 0.0 CB B:THR740 3.9 37.7 1.0 C B:THR740 3.9 34.5 1.0 CB B:PHE741 3.9 33.1 1.0 HB2 B:HIS673 3.9 38.8 0.0 CB B:HIS673 4.0 36.4 1.0 CB B:ALA609 4.0 36.8 1.0 HG22 B:THR740 4.0 41.5 0.0 HB3 B:ALA609 4.1 39.1 0.0 CA B:PHE741 4.1 34.2 1.0 CG B:PHE741 4.1 31.7 1.0 H B:LYS742 4.2 41.6 0.0 HG23 B:VAL677 4.2 30.0 0.0 HG21 B:VAL677 4.2 30.6 0.0 CG2 B:THR740 4.5 37.3 1.0 CE2 B:PHE741 4.5 31.8 1.0 HE2 B:PHE741 4.6 32.1 0.0 CG2 B:VAL677 4.6 29.3 1.0 HG22 B:VAL677 4.7 30.0 0.0 CG B:HIS673 4.7 39.3 1.0 CD B:GLN674 4.8 46.9 1.0 HA B:PHE741 4.8 36.1 0.0 O B:HIS673 4.9 31.4 1.0 HG21 B:THR740 4.9 42.5 0.0 HE22 B:GLN674 4.9 50.3 0.0 HB3 B:PHE741 4.9 34.9 0.0 N B:LYS742 4.9 38.0 1.0 C B:HIS673 4.9 32.4 1.0

Chlorine binding site 4 out of 4 in the The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 4 of The X-Ray Co-Crystal Structure of Human FGFR3 and Compound 17 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl1002 b:41.8 occ:1.00 CL1 B:WIQ1002 0.0 41.8 1.0 C15 B:WIQ1002 1.7 40.6 1.0 HG13 B:VAL486 2.4 74.2 0.0 C14 B:WIQ1002 2.7 39.6 1.0 C6 B:WIQ1002 2.7 41.4 1.0 HB2 B:LYS508 2.8 52.2 0.0 HG22 B:VAL555 3.0 45.1 0.0 HB1 B:ALA506 3.0 51.6 0.0 C5 B:WIQ1002 3.0 43.8 1.0 CG1 B:VAL486 3.4 69.9 1.0 HG21 B:VAL555 3.4 44.3 0.0 HG11 B:VAL486 3.4 73.7 0.0 HB3 B:ALA506 3.5 51.3 0.0 C B:VAL507 3.6 48.2 1.0 HG22 B:VAL486 3.6 73.3 0.0 N B:LYS508 3.6 48.5 1.0 CG2 B:VAL555 3.7 41.7 1.0 CB B:ALA506 3.7 47.1 1.0 C4 B:WIQ1002 3.8 46.2 1.0 CB B:LYS508 3.8 48.6 1.0 O B:VAL507 3.8 48.8 1.0 H B:LYS508 3.8 53.5 0.0 C B:ALA506 3.8 46.6 1.0 N B:VAL507 3.8 46.2 1.0 HA B:LYS508 3.9 54.3 0.0 C13 B:WIQ1002 4.0 39.4 1.0 CA B:LYS508 4.0 49.3 1.0 C7 B:WIQ1002 4.0 40.0 1.0 O B:ALA506 4.0 46.2 1.0 HG12 B:VAL486 4.1 74.8 0.0 CA B:VAL507 4.1 47.0 1.0 HG21 B:VAL486 4.2 72.9 0.0 H B:VAL507 4.2 52.2 0.0 CG2 B:VAL486 4.2 69.6 1.0 HA B:VAL507 4.2 52.6 0.0 HG23 B:VAL555 4.3 45.0 0.0 HA B:VAL486 4.3 74.2 0.0 CB B:VAL486 4.3 69.3 1.0 HB3 B:LYS508 4.4 52.7 0.0 CA B:ALA506 4.4 47.3 1.0 HD2 B:LYS508 4.5 54.0 0.0 HG13 B:VAL555 4.5 44.0 0.0 C8 B:WIQ1002 4.5 39.5 1.0 HB2 B:ALA506 4.6 51.9 0.0 H B:VAL555 4.7 45.5 0.0 O B:VAL553 4.7 43.9 1.0 HG3 B:LYS508 4.8 54.0 0.0 CG B:LYS508 4.8 50.0 1.0 HG11 B:VAL555 4.8 43.2 0.0 HD2 B:PHE483 4.8 87.1 0.0 C3 B:WIQ1002 4.9 49.6 1.0 N1 B:WIQ1002 4.9 48.6 1.0 CA B:VAL486 4.9 68.9 1.0 HA B:ALA506 4.9 53.3 0.0 CB B:VAL555 4.9 41.1 1.0 H B:VAL487 5.0 73.6 0.0 CG1 B:VAL555 5.0 40.8 1.0 HB3 B:PHE483 5.0 85.1 0.0

J.S.Tyhonas, L.D.Arnold, J.M.Cox, A.Franovic, E.Gardiner, K.Grandinetti, R.Kania, T.Kanouni, M.Lardy, C.Li, E.S.Martin, N.Miller, A.Mohan, E.A.Murphy, M.Perez, L.Soroceanu, N.Timple, S.Uryu, S.Womble, S.W.Kaldor. Discovery of Kin-3248, An Irreversible, Next Generation Fgfr Inhibitor For the Treatment of Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations. J.Med.Chem. 2024.
ISSN: ISSN 0022-2623
PubMed: 38267212
DOI: 10.1021/ACS.JMEDCHEM.3C01819