Chlorine in PDB 8xar: Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54

All present enzymatic activity of Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54:
2.5.1.6;

The structure of Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54, PDB code: 8xar was solved by J.Y.Zheng, G.P.Zhang, J.J.Li, S.L.Tong, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	47.12 / 1.19
Space group	I 2 2 2
Cell size a, b, c (Å), α, β, γ (°)	68.18, 94.16, 117.12, 90, 90, 90
R / Rfree (%)	11.1 / 13

The binding sites of Chlorine atom in the Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54 (pdb code 8xar). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 2 binding sites of Chlorine where determined in the Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54, PDB code: 8xar:
Jump to Chlorine binding site number: 1; 2;

Chlorine binding site 1 out of 2 in the Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl401 b:11.2 occ:1.00 CLAA A:YMW401 0.0 11.2 1.0 CAB A:YMW401 1.7 10.5 1.0 CAC A:YMW401 2.7 11.2 1.0 CAW A:YMW401 2.7 10.1 1.0 CAD A:YMW401 4.0 11.4 1.0 CAF A:YMW401 4.0 10.6 1.0 CAE A:YMW401 4.6 11.1 1.0 CE2 A:PHE20 4.6 10.3 1.0 CD2 A:PHE20 4.9 9.9 1.0

Chlorine binding site 2 out of 2 in the Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with Sam and Compound 54 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl406 b:13.1 occ:0.90 O A:HOH512 3.1 29.4 0.7 NE2 A:HIS29 3.1 10.6 1.0 NZ A:LYS181 3.2 11.2 1.0 NZ A:LYS265 3.2 12.9 1.0 O A:HOH689 3.4 28.8 0.6 CE1 A:HIS29 3.6 10.5 1.0 C5' A:SAM403 3.6 12.9 1.0 CE A:LYS265 3.7 12.4 1.0 C4' A:SAM403 3.8 11.1 1.0 O A:HOH962 3.9 43.5 1.0 CE A:LYS181 4.0 10.6 1.0 O A:HOH600 4.0 32.8 0.9 O A:HOH572 4.1 21.9 1.0 OD2 A:ASP258 4.1 16.1 1.0 OD2 A:ASP31 4.1 11.9 1.0 O3' A:SAM403 4.2 11.3 1.0 O A:HOH585 4.2 25.4 0.6 CD2 A:HIS29 4.3 9.8 1.0 CD A:LYS181 4.5 10.2 1.0 O A:HOH594 4.6 12.7 1.0 C3' A:SAM403 4.6 10.6 1.0 ND1 A:HIS29 4.9 10.3 1.0 O4' A:SAM403 4.9 10.5 1.0

J.Zheng, T.Zhang, S.Tong, T.Liu, J.Cui, H.Xu, D.Hu, Y.Shen, Y.Yin, D.Zhao, C.Tan, X.Dong, J.Chen, F.Ji, C.Tong, J.J.Li, J.Li, G.Zhang. Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with High Selectivity, Brain Penetration, and in Vivo Efficacy. J.Med.Chem. V. 67 9431 2024.
ISSN: ISSN 0022-2623
PubMed: 38818879
DOI: 10.1021/ACS.JMEDCHEM.4C00552