Chlorine in PDB 7qk4: Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683)

All present enzymatic activity of Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683):
2.1.1.356;

The structure of Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683), PDB code: 7qk4 was solved by K.Zhao, M.Zhao, X.Luo, H.Zhang, C.Scheufler, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	15.97 / 1.60
Space group	C 2 2 21
Cell size a, b, c (Å), α, β, γ (°)	50.456, 91.202, 179.016, 90, 90, 90
R / Rfree (%)	18.2 / 20.6

The structure of Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683) also contains other interesting chemical elements:

Fluorine

(F)

1 atom

The binding sites of Chlorine atom in the Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683) (pdb code 7qk4). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 3 binding sites of Chlorine where determined in the Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683), PDB code: 7qk4:
Jump to Chlorine binding site number: 1; 2; 3;

Chlorine binding site 1 out of 3 in the Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683)


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683) within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl501 b:20.8 occ:1.00 NH1 A:ARG269 3.2 20.1 1.0 N A:HIS295 3.4 16.5 1.0 O A:HOH846 3.5 29.5 1.0 O A:LYS293 3.6 19.2 1.0 CD2 A:PHE296 3.7 19.5 1.0 NH2 A:ARG269 3.7 20.7 1.0 CZ A:ARG269 3.9 20.6 1.0 O A:HOH703 4.0 32.3 1.0 CB A:HIS295 4.0 18.3 1.0 CE2 A:PHE296 4.1 20.8 1.0 CA A:ILE294 4.1 16.7 1.0 CA A:HIS295 4.2 16.8 1.0 C A:ILE294 4.2 17.2 1.0 N A:PHE296 4.4 17.3 1.0 CD2 A:HIS295 4.4 22.8 1.0 CG A:HIS295 4.6 21.1 1.0 C A:LYS293 4.6 19.2 1.0 C A:HIS295 4.7 17.7 1.0 CG A:PHE296 4.8 18.9 1.0 N A:ILE294 4.9 17.6 1.0

Chlorine binding site 2 out of 3 in the Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683)


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683) within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl502 b:16.5 occ:1.00 O A:HOH847 3.0 22.4 1.0 O A:HOH841 3.2 17.1 1.0 N A:TRP152 3.2 13.9 1.0 O A:HOH743 3.3 16.4 1.0 O A:HOH627 3.5 25.9 1.0 CD1 A:TRP152 3.6 16.0 1.0 O A:HOH745 3.7 19.2 1.0 CA A:ALA151 3.8 13.7 1.0 CB A:GLN100 3.8 11.4 1.0 NE2 A:GLN100 3.8 17.2 1.0 C A:ALA151 4.0 14.5 1.0 CB A:TRP152 4.0 13.9 1.0 CG A:GLN100 4.0 11.8 1.0 O A:HOH786 4.1 17.0 1.0 O A:PHE101 4.1 14.4 1.0 CA A:TRP152 4.2 13.6 1.0 CD A:GLN100 4.2 16.4 1.0 CG A:TRP152 4.2 15.2 1.0 CB A:ALA151 4.4 12.9 1.0 O A:TRP152 4.5 14.8 1.0 O A:HOH845 4.5 25.3 1.0 O A:CYS150 4.8 13.0 1.0 NE1 A:TRP152 4.8 15.4 1.0 C A:TRP152 4.8 14.1 1.0 N A:ALA151 4.9 13.8 1.0

Chlorine binding site 3 out of 3 in the Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683)


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of Eed in Complex with PRC2 Allosteric Inhibitor Compound 22 (MAK683) within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl503 b:24.6 occ:1.00 O A:HOH752 3.1 30.1 1.0 ND1 A:HIS305 3.1 19.0 1.0 O A:HOH661 3.2 16.3 1.0 O A:HOH622 3.3 27.1 1.0 O A:HOH802 3.3 33.1 1.0 CB A:GLU325 3.7 22.2 1.0 CG A:GLU325 3.8 29.5 1.0 CE1 A:HIS305 4.0 18.9 1.0 CB A:SER323 4.1 16.6 1.0 CG A:HIS305 4.1 18.0 1.0 CG2 A:VAL329 4.3 17.4 1.0 CB A:HIS305 4.3 19.5 1.0 CA A:HIS305 4.4 19.5 1.0 O A:ILE304 4.7 22.5 1.0 N A:GLU325 4.7 19.2 1.0 CA A:GLU325 4.7 19.4 1.0 OG A:SER323 4.8 17.8 1.0 N A:SER323 4.8 13.9 1.0 O A:ALA327 4.9 17.6 1.0 CA A:SER323 5.0 15.5 1.0

Y.Huang, M.Sendzik, J.Zhang, Z.Gao, Y.Sun, L.Wang, J.Gu, K.Zhao, Z.Yu, L.Zhang, Q.Zhang, J.Blanz, Z.Chen, V.Dubost, D.Fang, L.Feng, X.Fu, M.Kiffe, L.Li, F.Luo, X.Luo, Y.Mi, P.Mistry, D.Pearson, A.Piaia, C.Scheufler, R.Terranova, A.Weiss, J.Zeng, H.Zhang, J.Zhang, M.Zhao, M.P.Dillon, S.Jeay, W.Qi, J.Moggs, C.Pissot-Soldermann, E.Li, P.Atadja, A.Lingel, C.Oyang. Discovery of the Clinical Candidate MAK683: An Eed-Directed, Allosteric, and Selective PRC2 Inhibitor For the Treatment of Advanced Malignancies. J.Med.Chem. V. 65 5317 2022.
ISSN: ISSN 0022-2623
PubMed: 35352560
DOI: 10.1021/ACS.JMEDCHEM.1C02148