Chlorine in PDB 6wu8: Structure of Human SHP2 in Complex with Inhibitor Iacs-13909

All present enzymatic activity of Structure of Human SHP2 in Complex with Inhibitor Iacs-13909:
3.1.3.48;

The structure of Structure of Human SHP2 in Complex with Inhibitor Iacs-13909, PDB code: 6wu8 was solved by P.G.Leonard, S.Joseph, A.Rodenberger, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	42.13 / 2.40
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	54.671, 83.203, 217.701, 90, 90, 90
R / Rfree (%)	21 / 27

The binding sites of Chlorine atom in the Structure of Human SHP2 in Complex with Inhibitor Iacs-13909 (pdb code 6wu8). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 4 binding sites of Chlorine where determined in the Structure of Human SHP2 in Complex with Inhibitor Iacs-13909, PDB code: 6wu8:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine binding site 1 out of 4 in the Structure of Human SHP2 in Complex with Inhibitor Iacs-13909


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Structure of Human SHP2 in Complex with Inhibitor Iacs-13909 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:58.0 occ:1.00 CL7 A:U9Y601 0.0 58.0 1.0 C05 A:U9Y601 1.7 36.4 1.0 C04 A:U9Y601 2.6 35.6 1.0 C06 A:U9Y601 2.7 29.7 1.0 CL8 A:U9Y601 3.1 57.7 1.0 C09 A:U9Y601 3.1 30.9 1.0 N10 A:U9Y601 3.1 24.7 1.0 CG A:GLN257 3.4 36.7 1.0 CD A:ARG111 3.5 27.9 1.0 O A:THR253 3.8 29.5 1.0 CA A:LEU254 3.8 25.4 1.0 C01 A:U9Y601 3.9 32.3 1.0 C03 A:U9Y601 4.0 31.5 1.0 CB A:GLN257 4.0 32.1 1.0 CG A:ARG111 4.0 33.0 1.0 NE A:ARG111 4.1 35.6 1.0 CD1 A:LEU254 4.2 30.1 1.0 N11 A:U9Y601 4.2 24.0 1.0 C13 A:U9Y601 4.3 34.3 1.0 N A:LEU254 4.4 35.4 1.0 C A:THR253 4.4 28.7 1.0 C02 A:U9Y601 4.4 33.9 1.0 CB A:LEU254 4.5 25.8 1.0 O A:LEU254 4.6 23.9 1.0 C A:LEU254 4.7 26.7 1.0 CD A:GLN257 4.7 38.1 1.0 CZ A:ARG111 4.7 36.2 1.0 CG2 A:THR253 4.8 28.9 1.0 NH1 A:ARG111 4.9 35.1 1.0 C12 A:U9Y601 4.9 29.1 1.0

Chlorine binding site 2 out of 4 in the Structure of Human SHP2 in Complex with Inhibitor Iacs-13909


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Structure of Human SHP2 in Complex with Inhibitor Iacs-13909 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:57.7 occ:1.00 CL8 A:U9Y601 0.0 57.7 1.0 C04 A:U9Y601 1.7 35.6 1.0 C03 A:U9Y601 2.6 31.5 1.0 C05 A:U9Y601 2.7 36.4 1.0 CL7 A:U9Y601 3.1 58.0 1.0 CG A:GLN495 3.4 25.9 1.0 CB A:GLN495 3.8 31.2 1.0 CD A:GLN495 3.9 31.5 1.0 NH1 A:ARG111 3.9 35.1 1.0 C02 A:U9Y601 3.9 33.9 1.0 C06 A:U9Y601 4.1 29.7 1.0 NE2 A:GLN495 4.2 31.9 1.0 CG A:GLN257 4.3 36.7 1.0 CB A:GLN257 4.3 32.1 1.0 CD A:ARG111 4.4 27.9 1.0 C01 A:U9Y601 4.5 32.3 1.0 OE1 A:GLN495 4.5 31.3 1.0 CZ A:ARG111 4.6 36.2 1.0 NE A:ARG111 4.8 35.6 1.0

Chlorine binding site 3 out of 4 in the Structure of Human SHP2 in Complex with Inhibitor Iacs-13909


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of Structure of Human SHP2 in Complex with Inhibitor Iacs-13909 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:63.1 occ:1.00 CL7 B:U9Y601 0.0 63.1 1.0 C05 B:U9Y601 1.7 31.7 1.0 C04 B:U9Y601 2.6 34.9 1.0 C06 B:U9Y601 2.7 30.5 1.0 CL8 B:U9Y601 3.1 58.4 1.0 C09 B:U9Y601 3.1 26.7 1.0 N10 B:U9Y601 3.2 26.9 1.0 CG B:GLN257 3.4 31.1 1.0 CD B:ARG111 3.5 28.5 1.0 CA B:LEU254 3.8 32.4 1.0 CD1 B:LEU254 3.9 28.9 1.0 C01 B:U9Y601 3.9 22.7 1.0 CG B:ARG111 4.0 32.0 1.0 C03 B:U9Y601 4.0 27.6 1.0 CB B:GLN257 4.0 28.4 1.0 NE B:ARG111 4.1 29.6 1.0 O B:THR253 4.1 28.8 1.0 C13 B:U9Y601 4.2 28.5 1.0 N11 B:U9Y601 4.3 27.8 1.0 CB B:LEU254 4.3 34.0 1.0 N B:LEU254 4.3 40.4 1.0 C02 B:U9Y601 4.4 26.4 1.0 C B:THR253 4.5 32.6 1.0 O B:LEU254 4.6 28.4 1.0 CD B:GLN257 4.6 35.0 1.0 C B:LEU254 4.7 28.0 1.0 CG B:LEU254 4.7 31.1 1.0 CZ B:ARG111 4.8 37.0 1.0 CG2 B:THR253 4.9 25.1 1.0 C12 B:U9Y601 4.9 29.0 1.0 O B:HOH733 5.0 37.4 1.0

Chlorine binding site 4 out of 4 in the Structure of Human SHP2 in Complex with Inhibitor Iacs-13909


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 4 of Structure of Human SHP2 in Complex with Inhibitor Iacs-13909 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:58.4 occ:1.00 CL8 B:U9Y601 0.0 58.4 1.0 C04 B:U9Y601 1.7 34.9 1.0 C03 B:U9Y601 2.7 27.6 1.0 C05 B:U9Y601 2.7 31.7 1.0 CL7 B:U9Y601 3.1 63.1 1.0 CG B:GLN495 3.4 24.9 1.0 CD B:GLN495 3.7 31.6 1.0 CB B:GLN495 3.8 28.1 1.0 NE2 B:GLN495 3.8 32.2 1.0 C02 B:U9Y601 3.9 26.4 1.0 C06 B:U9Y601 4.1 30.5 1.0 CG B:GLN257 4.1 31.1 1.0 NH1 B:ARG111 4.2 32.5 1.0 CB B:GLN257 4.3 28.4 1.0 OE1 B:GLN495 4.4 28.6 1.0 NE2 B:GLN257 4.4 35.5 1.0 CD B:ARG111 4.4 28.5 1.0 C01 B:U9Y601 4.4 22.7 1.0 CZ B:ARG111 4.7 37.0 1.0 NE B:ARG111 4.7 29.6 1.0 CD B:GLN257 4.8 35.0 1.0

Y.Sun, B.A.Meyers, B.Czako, P.Leonard, F.Mseeh, A.L.Harris, Q.Wu, S.Johnson, C.A.Parker, J.B.Cross, M.E.Di Francesco, B.J.Bivona, C.A.Bristow, J.P.Burke, C.C.Carrillo, C.L.Carroll, Q.Chang, N.Feng, G.Gao, S.Gera, V.Giuliani, J.K.Huang, Y.Jiang, Z.Kang, J.J.Kovacs, C.Y.Liu, A.M.Lopez, X.Ma, P.K.Mandal, T.Mcafoos, M.A.Miller, R.A.Mullinax, M.Peoples, V.Ramamoorthy, S.Seth, N.D.Spencer, E.Suzuki, C.C.Williams, S.S.Yu, A.M.Zuniga, G.F.Draetta, J.R.Marszalek, T.P.Heffernan, N.E.Kohl, P.Jones. Allosteric SHP2 Inhibitor, Iacs-13909, Overcomes Egfr-Dependent and Egfr-Independent Resistance Mechanisms Toward Osimertinib. Cancer Res. V. 80 4840 2020.
ISSN: ESSN 1538-7445
PubMed: 32928921
DOI: 10.1158/0008-5472.CAN-20-1634