Chlorine in PDB 6md9: Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3

All present enzymatic activity of Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3:
3.1.3.48;

The structure of Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3, PDB code: 6md9 was solved by M.Fodor, T.Stams, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	21.40 / 2.12
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	46.340, 213.960, 55.830, 90.00, 96.69, 90.00
R / Rfree (%)	21.8 / 27.2

The binding sites of Chlorine atom in the Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3 (pdb code 6md9). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 2 binding sites of Chlorine where determined in the Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3, PDB code: 6md9:
Jump to Chlorine binding site number: 1; 2;

Chlorine binding site 1 out of 2 in the Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:42.4 occ:1.00 CL1 A:JEJ601 0.0 42.4 1.0 C22 A:JEJ601 1.7 37.1 1.0 C1 A:JEJ601 2.7 34.1 1.0 C5 A:JEJ601 2.7 35.4 1.0 O A:HOH756 3.0 56.8 1.0 OG1 A:THR219 3.1 29.8 1.0 C6 A:JEJ601 3.1 35.4 1.0 O2 A:JEJ601 3.2 31.5 1.0 C11 A:JEJ601 3.4 36.5 1.0 C10 A:JEJ601 3.5 34.0 1.0 CG A:PRO491 3.7 28.5 1.0 N A:LYS492 3.8 23.4 1.0 CB A:PRO491 4.0 25.1 1.0 C2 A:JEJ601 4.0 35.2 1.0 N1 A:JEJ601 4.0 36.2 1.0 OD1 A:ASP489 4.0 27.1 1.0 C4 A:JEJ601 4.0 32.5 1.0 CA A:LYS492 4.1 24.2 1.0 CB A:THR219 4.1 34.6 1.0 CB A:LYS492 4.2 26.5 1.0 ND2 A:ASN217 4.2 45.9 1.0 CG2 A:THR219 4.2 33.1 1.0 C A:PRO491 4.3 25.1 1.0 C7 A:JEJ601 4.4 40.3 1.0 OD2 A:ASP489 4.4 29.3 1.0 C3 A:JEJ601 4.5 35.7 1.0 CG A:ASP489 4.6 26.5 1.0 N2 A:JEJ601 4.6 38.0 1.0 CA A:PRO491 4.7 23.2 1.0 O1 A:JEJ601 4.8 38.4 1.0 NH2 A:ARG111 4.8 47.3 1.0 CD A:PRO491 4.8 24.4 1.0 O A:PRO491 4.9 21.6 1.0 CG A:LYS492 5.0 36.4 1.0

Chlorine binding site 2 out of 2 in the Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Non-Receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Isoxazolo-Pyridinone 3 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:41.6 occ:1.00 CL1 B:JEJ601 0.0 41.6 1.0 C22 B:JEJ601 1.7 41.5 1.0 C1 B:JEJ601 2.7 41.7 1.0 C5 B:JEJ601 2.8 38.7 1.0 OG1 B:THR219 3.1 31.3 1.0 C6 B:JEJ601 3.2 37.0 1.0 O2 B:JEJ601 3.3 29.9 1.0 C11 B:JEJ601 3.5 36.2 1.0 O B:HOH728 3.6 28.0 1.0 C10 B:JEJ601 3.7 33.2 1.0 CG B:PRO491 3.7 33.0 1.0 OD1 B:ASP489 3.7 24.7 1.0 N B:LYS492 3.9 24.4 1.0 C2 B:JEJ601 4.0 41.2 1.0 ND2 B:ASN217 4.0 47.1 1.0 C4 B:JEJ601 4.1 38.4 1.0 N1 B:JEJ601 4.1 37.9 1.0 CB B:LYS492 4.1 24.1 1.0 CB B:PRO491 4.1 28.8 1.0 CA B:LYS492 4.2 23.5 1.0 OD2 B:ASP489 4.2 35.4 1.0 CB B:THR219 4.3 32.6 1.0 CG2 B:THR219 4.4 29.2 1.0 CG B:ASP489 4.4 27.9 1.0 C B:PRO491 4.4 27.7 1.0 C7 B:JEJ601 4.5 37.1 1.0 C3 B:JEJ601 4.6 39.4 1.0 O B:HOH836 4.8 37.6 1.0 N2 B:JEJ601 4.8 37.7 1.0 CA B:PRO491 4.8 26.9 1.0 O1 B:JEJ601 4.9 34.9 1.0 CD B:PRO491 4.9 28.6 1.0 CG B:LYS492 4.9 30.5 1.0

J.T.Bagdanoff, Z.Chen, M.Acker, Y.N.Chen, H.Chan, M.Dore, B.Firestone, M.Fodor, J.Fortanet, M.Hentemann, M.Kato, R.Koenig, L.R.Labonte, S.Liu, M.Mohseni, R.Ntaganda, P.Sarver, T.Smith, M.Sendzik, T.Stams, S.Spence, C.Towler, H.Wang, P.Wang, S.L.Williams, M.J.Lamarche. Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors. J. Med. Chem. V. 62 1781 2019.
ISSN: ISSN 1520-4804
PubMed: 30688462
DOI: 10.1021/ACS.JMEDCHEM.8B01725