Chlorine in PDB 7r7i: Structure of Human SHP2 in Complex with Compound 27

All present enzymatic activity of Structure of Human SHP2 in Complex with Compound 27:
3.1.3.48;

The structure of Structure of Human SHP2 in Complex with Compound 27, PDB code: 7r7i was solved by P.G.Leonard, J.Cross, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	54.78 / 2.85
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	55.18, 83.63, 217.49, 90, 90, 90
R / Rfree (%)	23.2 / 29.2

The binding sites of Chlorine atom in the Structure of Human SHP2 in Complex with Compound 27 (pdb code 7r7i). 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 Compound 27, PDB code: 7r7i:
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 Compound 27


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 Compound 27 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:38.3 occ:1.00 CL15 A:3CW601 0.0 38.3 1.0 C14 A:3CW601 1.8 37.4 1.0 C13 A:3CW601 2.8 36.7 1.0 C09 A:3CW601 2.8 35.7 1.0 CL16 A:3CW601 3.1 47.0 1.0 C01 A:3CW601 3.2 36.5 1.0 C08 A:3CW601 3.3 30.1 1.0 C06 A:3CW601 3.4 34.9 1.0 CG A:GLN257 3.4 34.9 1.0 CG A:ARG111 3.5 31.8 1.0 NE A:ARG111 3.8 39.0 1.0 O A:THR253 3.8 37.8 1.0 CD A:GLN257 3.9 40.2 1.0 NE2 A:GLN257 4.0 43.5 1.0 CD A:ARG111 4.0 32.5 1.0 CA A:LEU254 4.0 29.6 1.0 C12 A:3CW601 4.1 33.0 1.0 C10 A:3CW601 4.1 36.4 1.0 N02 A:3CW601 4.1 38.7 1.0 C A:THR253 4.2 33.9 1.0 CG2 A:THR253 4.3 31.4 1.0 CZ A:ARG111 4.3 37.5 1.0 N A:LEU254 4.3 36.5 1.0 N05 A:3CW601 4.4 37.5 1.0 C11 A:3CW601 4.6 35.0 1.0 CB A:GLN257 4.7 33.5 1.0 OE1 A:GLN257 4.7 34.1 1.0 NH2 A:ARG111 4.7 37.0 1.0 CB A:LEU254 4.8 31.4 1.0 CD1 A:LEU254 4.8 33.1 1.0 CB A:ARG111 4.9 34.0 1.0 NH1 A:ARG111 5.0 39.2 1.0 C03 A:3CW601 5.0 38.4 1.0

Chlorine binding site 2 out of 4 in the Structure of Human SHP2 in Complex with Compound 27


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 Compound 27 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:47.0 occ:1.00 CL16 A:3CW601 0.0 47.0 1.0 C13 A:3CW601 1.8 36.7 1.0 C14 A:3CW601 2.8 37.4 1.0 C12 A:3CW601 2.8 33.0 1.0 CL15 A:3CW601 3.1 38.3 1.0 CG A:GLN495 3.3 31.4 1.0 CG A:GLN257 3.6 34.9 1.0 CD A:GLN495 3.9 27.6 1.0 CB A:GLN495 3.9 25.4 1.0 CB A:GLN257 3.9 33.5 1.0 NE A:ARG111 4.1 39.0 1.0 C09 A:3CW601 4.1 35.7 1.0 C11 A:3CW601 4.1 35.0 1.0 OE1 A:GLN495 4.2 28.9 1.0 NH2 A:ARG111 4.2 37.0 1.0 CD1 A:LEU254 4.3 33.1 1.0 CD A:GLN257 4.5 40.2 1.0 CZ A:ARG111 4.5 37.5 1.0 NE2 A:GLN495 4.6 27.1 1.0 C10 A:3CW601 4.6 36.4 1.0 OE1 A:GLN257 4.7 34.1 1.0 O A:PRO491 4.8 28.7 1.0

Chlorine binding site 3 out of 4 in the Structure of Human SHP2 in Complex with Compound 27


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 Compound 27 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:46.6 occ:1.00 CL15 B:3CW601 0.0 46.6 1.0 C14 B:3CW601 1.8 30.7 1.0 C13 B:3CW601 2.8 27.2 1.0 C09 B:3CW601 2.8 27.3 1.0 C01 B:3CW601 3.1 35.4 1.0 CL16 B:3CW601 3.2 45.1 1.0 C08 B:3CW601 3.3 30.1 1.0 C06 B:3CW601 3.4 32.5 1.0 O B:THR253 3.4 40.3 1.0 CG B:GLN257 3.4 37.1 1.0 CG B:ARG111 3.5 30.4 1.0 CD B:ARG111 3.6 32.8 1.0 NE B:ARG111 3.7 37.8 1.0 CA B:LEU254 3.8 35.4 1.0 C B:THR253 3.9 33.1 1.0 N02 B:3CW601 4.0 39.5 1.0 C12 B:3CW601 4.1 26.4 1.0 N B:LEU254 4.1 36.2 1.0 C10 B:3CW601 4.1 28.5 1.0 CG2 B:THR253 4.1 33.3 1.0 CD B:GLN257 4.2 38.0 1.0 NE2 B:GLN257 4.4 36.7 1.0 N05 B:3CW601 4.4 35.2 1.0 CB B:LEU254 4.4 45.4 1.0 CB B:GLN257 4.5 34.9 1.0 CD1 B:LEU254 4.6 34.0 1.0 CZ B:ARG111 4.6 44.3 1.0 C11 B:3CW601 4.6 29.2 1.0 CB B:ARG111 4.6 26.1 1.0 C03 B:3CW601 4.8 37.7 1.0 C B:LEU254 4.9 34.1 1.0 CB B:THR253 4.9 32.3 1.0

Chlorine binding site 4 out of 4 in the Structure of Human SHP2 in Complex with Compound 27


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 Compound 27 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:45.1 occ:1.00 CL16 B:3CW601 0.0 45.1 1.0 C13 B:3CW601 1.8 27.2 1.0 C12 B:3CW601 2.8 26.4 1.0 C14 B:3CW601 2.8 30.7 1.0 CL15 B:3CW601 3.2 46.6 1.0 CD B:GLN495 3.4 34.0 1.0 CG B:GLN495 3.4 27.9 1.0 CG B:GLN257 3.5 37.1 1.0 CB B:GLN257 3.5 34.9 1.0 CD1 B:LEU254 3.6 34.0 1.0 OE1 B:GLN495 3.7 34.2 1.0 CB B:GLN495 3.7 25.1 1.0 NE2 B:GLN495 3.8 33.4 1.0 C11 B:3CW601 4.1 29.2 1.0 C09 B:3CW601 4.1 27.3 1.0 CD B:GLN257 4.5 38.0 1.0 CZ B:ARG111 4.5 44.3 1.0 NE B:ARG111 4.6 37.8 1.0 C10 B:3CW601 4.6 28.5 1.0 NH2 B:ARG111 4.7 30.9 1.0 OE1 B:GLN257 4.7 32.1 1.0 NH1 B:ARG111 4.8 57.9 1.0 O B:LEU254 4.8 40.6 1.0 CG B:LEU254 4.8 40.9 1.0 CA B:LEU254 4.9 35.4 1.0 CD B:ARG111 4.9 32.8 1.0 O B:PRO491 5.0 25.8 1.0

B.Czako, Y.Sun, T.Mcafoos, J.B.Cross, P.G.Leonard, J.P.Burke, C.L.Carroll, N.Feng, A.L.Harris, Y.Jiang, Z.Kang, J.J.Kovacs, P.Mandal, B.A.Meyers, F.Mseeh, C.A.Parker, S.S.Yu, C.C.Williams, Q.Wu, M.E.Di Francesco, G.Draetta, T.Heffernan, J.R.Marszalek, N.E.Kohl, P.Jones. Discovery of 6-[(3 S ,4 S )-4-Amino-3-Methyl-2-Oxa-8-Azaspiro[4.5]Decan-8-Yl]-3-(2, 3-Dichlorophenyl)-2-Methyl-3,4-Dihydropyrimidin-4-One (Iacs-15414), A Potent and Orally Bioavailable SHP2 Inhibitor. J.Med.Chem. 2021.
ISSN: ISSN 0022-2623
PubMed: 34643390
DOI: 10.1021/ACS.JMEDCHEM.1C01132