Chlorine in PDB 7xhq: Small-Molecule Allosteric Regulation Mechanism of SHP2

All present enzymatic activity of Small-Molecule Allosteric Regulation Mechanism of SHP2:
3.1.3.48;

The structure of Small-Molecule Allosteric Regulation Mechanism of SHP2, PDB code: 7xhq was solved by Y.Luo, J.Zhu, K.Yu, B.Liu, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	38.61 / 2.20
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	55.69, 91.39, 212.979, 90, 90, 90
R / Rfree (%)	23.9 / 27.5

The binding sites of Chlorine atom in the Small-Molecule Allosteric Regulation Mechanism of SHP2 (pdb code 7xhq). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 4 binding sites of Chlorine where determined in the Small-Molecule Allosteric Regulation Mechanism of SHP2, PDB code: 7xhq:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine binding site 1 out of 4 in the Small-Molecule Allosteric Regulation Mechanism of SHP2


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Small-Molecule Allosteric Regulation Mechanism of SHP2 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:42.1 occ:1.00 CL1 A:FIZ601 0.0 42.1 1.0 C1 A:FIZ601 1.8 29.1 1.0 C2 A:FIZ601 2.8 27.8 1.0 C6 A:FIZ601 2.9 31.4 1.0 C7 A:FIZ601 3.1 27.6 1.0 C8 A:FIZ601 3.2 26.1 1.0 CD A:ARG111 3.2 31.5 1.0 CG A:GLN257 3.3 30.7 1.0 CL2 A:FIZ601 3.3 53.7 1.0 O A:THR253 3.7 27.3 1.0 CB A:GLN257 3.8 33.3 1.0 CD1 A:LEU254 3.8 29.3 1.0 CA A:LEU254 3.9 27.5 1.0 NE A:ARG111 3.9 30.7 1.0 C3 A:FIZ601 4.1 29.4 1.0 CG A:ARG111 4.1 31.9 1.0 C5 A:FIZ601 4.2 33.1 1.0 C11 A:FIZ601 4.2 31.2 1.0 C9 A:FIZ601 4.3 28.3 1.0 O A:LEU254 4.4 29.5 1.0 C A:THR253 4.4 30.0 1.0 N A:LEU254 4.5 27.0 1.0 C A:LEU254 4.6 27.6 1.0 C4 A:FIZ601 4.6 30.4 1.0 CD A:GLN257 4.6 36.5 1.0 CZ A:ARG111 4.7 29.1 1.0 CB A:LEU254 4.7 28.7 1.0 O A:HOH730 4.7 28.9 1.0 N10 A:FIZ601 4.8 32.3 1.0 CG A:LEU254 4.9 25.7 1.0 CG2 A:THR253 4.9 31.1 1.0 OE1 A:GLN495 4.9 33.2 1.0 NH1 A:ARG111 4.9 27.6 1.0 CD A:GLN495 5.0 32.4 1.0

Chlorine binding site 2 out of 4 in the Small-Molecule Allosteric Regulation Mechanism of SHP2


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Small-Molecule Allosteric Regulation Mechanism of SHP2 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl601 b:53.7 occ:1.00 CL2 A:FIZ601 0.0 53.7 1.0 C6 A:FIZ601 1.8 31.4 1.0 C5 A:FIZ601 2.8 33.1 1.0 C1 A:FIZ601 2.8 29.1 1.0 CG A:GLN495 3.3 23.6 1.0 CL1 A:FIZ601 3.3 42.1 1.0 O A:HOH830 3.4 40.4 1.0 CD A:GLN495 3.7 32.4 1.0 NE2 A:GLN495 3.7 31.6 1.0 CB A:GLN495 4.0 26.3 1.0 C4 A:FIZ601 4.1 30.4 1.0 NE A:ARG111 4.1 30.7 1.0 CZ A:ARG111 4.2 29.1 1.0 C2 A:FIZ601 4.2 27.8 1.0 NH2 A:ARG111 4.3 36.1 1.0 CB A:GLN257 4.5 33.3 1.0 OE1 A:GLN495 4.5 33.2 1.0 CG A:GLN257 4.5 30.7 1.0 C3 A:FIZ601 4.6 29.4 1.0 CD A:ARG111 4.6 31.5 1.0 NH1 A:ARG111 4.7 27.6 1.0

Chlorine binding site 3 out of 4 in the Small-Molecule Allosteric Regulation Mechanism of SHP2


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of Small-Molecule Allosteric Regulation Mechanism of SHP2 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:44.2 occ:1.00 CL1 B:FIZ601 0.0 44.2 1.0 C1 B:FIZ601 1.8 26.7 1.0 C2 B:FIZ601 2.8 26.4 1.0 C6 B:FIZ601 2.9 29.0 1.0 C7 B:FIZ601 3.1 27.0 1.0 CG B:GLN257 3.3 29.9 1.0 CL2 B:FIZ601 3.3 54.2 1.0 C8 B:FIZ601 3.3 26.1 1.0 CD B:ARG111 3.5 28.8 1.0 O B:THR253 3.7 28.2 1.0 CB B:GLN257 3.8 31.1 1.0 CA B:LEU254 3.8 25.9 1.0 CG B:ARG111 3.9 29.2 1.0 NE B:ARG111 3.9 28.8 1.0 CD1 B:LEU254 4.0 23.7 1.0 C3 B:FIZ601 4.1 25.7 1.0 C5 B:FIZ601 4.1 29.6 1.0 C11 B:FIZ601 4.2 30.7 1.0 C B:THR253 4.3 27.1 1.0 O B:LEU254 4.3 29.2 1.0 N B:LEU254 4.4 28.2 1.0 C9 B:FIZ601 4.4 27.5 1.0 C B:LEU254 4.5 27.8 1.0 CB B:LEU254 4.5 29.1 1.0 CD B:GLN257 4.6 31.3 1.0 C4 B:FIZ601 4.6 31.7 1.0 CZ B:ARG111 4.7 29.6 1.0 N10 B:FIZ601 4.8 31.6 1.0 CG2 B:THR253 4.8 28.7 1.0 OE1 B:GLN495 4.9 28.6 1.0 CG B:LEU254 4.9 26.8 1.0 CD B:GLN495 4.9 26.8 1.0

Chlorine binding site 4 out of 4 in the Small-Molecule Allosteric Regulation Mechanism of SHP2


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 4 of Small-Molecule Allosteric Regulation Mechanism of SHP2 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl601 b:54.2 occ:1.00 CL2 B:FIZ601 0.0 54.2 1.0 C6 B:FIZ601 1.8 29.0 1.0 C5 B:FIZ601 2.8 29.6 1.0 C1 B:FIZ601 2.8 26.7 1.0 CL1 B:FIZ601 3.3 44.2 1.0 CG B:GLN495 3.4 26.9 1.0 CD B:GLN495 3.7 26.8 1.0 NE2 B:GLN495 3.7 24.5 1.0 NH1 B:ARG111 4.0 32.5 1.0 C4 B:FIZ601 4.1 31.7 1.0 CZ B:ARG111 4.1 29.6 1.0 CB B:GLN495 4.1 25.9 1.0 C2 B:FIZ601 4.2 26.4 1.0 NE B:ARG111 4.3 28.8 1.0 CB B:GLN257 4.4 31.1 1.0 CD B:ARG111 4.5 28.8 1.0 OE1 B:GLN495 4.5 28.6 1.0 CG B:GLN257 4.5 29.9 1.0 NH2 B:ARG111 4.6 27.9 1.0 C3 B:FIZ601 4.6 25.7 1.0

Y.Luo, J.Li, Y.Zong, M.Sun, W.Zheng, J.Zhu, L.Liu, B.Liu. Discovery of the SHP2 Allosteric Inhibitor 2-((3R,4R)-4-Amino-3-Methyl-2-Oxa-8-Azaspiro[4.5]Decan-8-Yl) -5-(2,3-Dichlorophenyl)-3-Methylpyrrolo[2,1-F][1,2,4] Triazin-4(3H)-One. J Enzyme Inhib Med Chem V. 38 398 2023.
ISSN: ESSN 1475-6374
PubMed: 36476046
DOI: 10.1080/14756366.2022.2151594