Chlorine in PDB 8cbh: SHP2 in Complex with A Novel Allosteric Inhibitor

All present enzymatic activity of SHP2 in Complex with A Novel Allosteric Inhibitor:
3.1.3.48;

The structure of SHP2 in Complex with A Novel Allosteric Inhibitor, PDB code: 8cbh was solved by R.Di Fabio, A.Petrocchi, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	107.98 / 2.24
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	44.888, 215.966, 55.829, 90, 95.11, 90
R / Rfree (%)	21.6 / 26.4

The binding sites of Chlorine atom in the SHP2 in Complex with A Novel Allosteric Inhibitor (pdb code 8cbh). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 4 binding sites of Chlorine where determined in the SHP2 in Complex with A Novel Allosteric Inhibitor, PDB code: 8cbh:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine binding site 1 out of 4 in the SHP2 in Complex with A Novel Allosteric Inhibitor


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of SHP2 in Complex with A Novel Allosteric Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:53.9 occ:1.00 CL1 A:U70601 0.0 53.9 1.0 C2 A:U70601 1.7 29.9 1.0 C7 A:U70601 2.7 30.3 1.0 C3 A:U70601 2.7 25.1 1.0 CL8 A:U70601 3.1 42.0 1.0 CG A:GLN495 3.5 30.5 1.0 CB A:GLN495 3.8 29.2 1.0 O A:HOH794 4.0 24.9 1.0 C4 A:U70601 4.0 26.1 1.0 C6 A:U70601 4.0 26.8 1.0 CD A:GLN495 4.2 31.3 1.0 NE A:ARG111 4.3 49.1 1.0 C5 A:U70601 4.5 25.8 1.0 NH2 A:ARG111 4.5 50.7 1.0 NE2 A:GLN495 4.6 32.7 1.0 CZ A:ARG111 4.6 49.5 1.0 OE1 A:GLN495 4.8 32.1 1.0 CG A:GLN257 4.9 38.3 1.0 CD A:ARG111 5.0 48.3 1.0

Chlorine binding site 2 out of 4 in the SHP2 in Complex with A Novel Allosteric Inhibitor


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of SHP2 in Complex with A Novel Allosteric Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:42.0 occ:1.00 CL8 A:U70601 0.0 42.0 1.0 C7 A:U70601 1.7 30.3 1.0 C2 A:U70601 2.7 29.9 1.0 C6 A:U70601 2.7 26.8 1.0 CL1 A:U70601 3.1 53.9 1.0 C9 A:U70601 3.1 26.3 1.0 N10 A:U70601 3.2 26.4 1.0 CG A:GLN257 3.4 38.3 1.0 CD1 A:LEU254 3.6 30.9 1.0 CD A:ARG111 3.6 48.3 1.0 NE A:ARG111 3.9 49.1 1.0 CA A:LEU254 4.0 32.6 1.0 C5 A:U70601 4.0 25.8 1.0 C3 A:U70601 4.0 25.1 1.0 CB A:GLN257 4.0 37.8 1.0 C18 A:U70601 4.3 32.4 1.0 O A:THR253 4.3 33.2 1.0 N11 A:U70601 4.4 27.4 1.0 CB A:LEU254 4.5 32.3 1.0 CD A:GLN257 4.5 39.5 1.0 C4 A:U70601 4.5 26.1 1.0 CG A:ARG111 4.6 44.9 1.0 N A:LEU254 4.6 33.8 1.0 CG A:LEU254 4.6 30.9 1.0 O A:LEU254 4.7 32.0 1.0 OE1 A:GLN495 4.7 32.1 1.0 C A:THR253 4.8 34.2 1.0 CZ A:ARG111 4.8 49.5 1.0 CD A:GLN495 4.8 31.3 1.0 C A:LEU254 4.9 32.3 1.0 CG A:GLN495 4.9 30.5 1.0 C13 A:U70601 4.9 30.6 1.0 CB A:GLN495 4.9 29.2 1.0

Chlorine binding site 3 out of 4 in the SHP2 in Complex with A Novel Allosteric Inhibitor


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of SHP2 in Complex with A Novel Allosteric Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:49.0 occ:1.00 CL1 B:U70601 0.0 49.0 1.0 C2 B:U70601 1.7 32.3 1.0 C7 B:U70601 2.7 34.4 1.0 C3 B:U70601 2.7 26.1 1.0 CL8 B:U70601 3.1 54.0 1.0 CG B:GLN495 3.4 28.7 1.0 CB B:GLN495 3.8 28.0 1.0 CD B:GLN495 3.9 29.0 1.0 C6 B:U70601 4.0 31.1 1.0 C4 B:U70601 4.0 26.0 1.0 NE B:ARG111 4.2 48.8 1.0 NE2 B:GLN495 4.3 30.0 1.0 CG B:GLN257 4.4 37.0 1.0 OE1 B:GLN495 4.5 28.7 1.0 C5 B:U70601 4.5 27.7 1.0 CD B:ARG111 4.6 48.2 1.0 CB B:GLN257 4.7 36.3 1.0 CZ B:ARG111 4.8 50.4 1.0 OE1 B:GLN257 5.0 38.0 1.0

Chlorine binding site 4 out of 4 in the SHP2 in Complex with A Novel Allosteric Inhibitor


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 4 of SHP2 in Complex with A Novel Allosteric Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:54.0 occ:1.00 CL8 B:U70601 0.0 54.0 1.0 C7 B:U70601 1.7 34.4 1.0 C6 B:U70601 2.7 31.1 1.0 C2 B:U70601 2.7 32.3 1.0 C9 B:U70601 3.0 31.5 1.0 CL1 B:U70601 3.1 49.0 1.0 N10 B:U70601 3.1 31.4 1.0 CG B:GLN257 3.4 37.0 1.0 CD B:ARG111 3.4 48.2 1.0 CA B:LEU254 3.7 33.8 1.0 CD1 B:LEU254 3.8 32.4 1.0 O B:THR253 3.9 35.4 1.0 C5 B:U70601 4.0 27.7 1.0 C3 B:U70601 4.0 26.1 1.0 NE B:ARG111 4.1 48.8 1.0 CB B:GLN257 4.1 36.3 1.0 C18 B:U70601 4.2 37.4 1.0 N11 B:U70601 4.3 32.5 1.0 N B:LEU254 4.3 35.5 1.0 CB B:LEU254 4.4 33.8 1.0 C B:THR253 4.4 36.4 1.0 CD B:GLN257 4.5 38.4 1.0 C4 B:U70601 4.5 26.0 1.0 O B:LEU254 4.6 32.1 1.0 CG B:ARG111 4.6 45.2 1.0 C B:LEU254 4.7 33.1 1.0 CG B:LEU254 4.7 32.6 1.0 C13 B:U70601 4.8 34.7 1.0 OE1 B:GLN495 4.8 28.7 1.0 CG2 B:THR253 4.8 39.4 1.0 CZ B:ARG111 4.9 50.4 1.0 CD B:GLN495 5.0 29.0 1.0

E.Torrente, V.Fodale, A.Ciammaichella, F.Ferrigno, J.M.Ontoria, S.Ponzi, I.Rossetti, A.Sferrazza, J.Amaudrut, A.Missineo, S.Esposito, S.Palombo, M.Nibbio, M.Cerretani, M.Bisbocci, A.Cellucci, A.Di Marco, C.Alli, V.Pucci, C.Toniatti, A.Petrocchi. Discovery of A Novel Series of Imidazopyrazine Derivatives As Potent SHP2 Allosteric Inhibitors. Acs Med.Chem.Lett. V. 14 156 2023.
ISSN: ISSN 1948-5875
PubMed: 36793438
DOI: 10.1021/ACSMEDCHEMLETT.2C00454