Chlorine in PDB 6c4d: Structure Based Design of RIP1 Kinase Inhibitors

All present enzymatic activity of Structure Based Design of RIP1 Kinase Inhibitors:
2.7.11.1;

The structure of Structure Based Design of RIP1 Kinase Inhibitors, PDB code: 6c4d was solved by K.S.Saikatendu, M.Yoshikawa, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	95.39 / 2.52
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	45.768, 138.133, 95.933, 90.00, 96.08, 90.00
R / Rfree (%)	23.6 / 29.6

The binding sites of Chlorine atom in the Structure Based Design of RIP1 Kinase Inhibitors (pdb code 6c4d). 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 Based Design of RIP1 Kinase Inhibitors, PDB code: 6c4d:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine binding site 1 out of 4 in the Structure Based Design of RIP1 Kinase Inhibitors


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 of RIP1 Kinase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl1100 b:62.2 occ:1.00 CL1 A:EJP1100 0.0 62.2 1.0 C16 A:EJP1100 1.7 64.6 1.0 N3 A:EJP1100 2.7 62.2 1.0 C11 A:EJP1100 2.8 65.5 1.0 C24 A:EJP1100 3.2 60.2 1.0 O A:VAL76 3.3 65.0 1.0 O A:MET67 3.5 73.0 1.0 C6 A:EJP1100 3.6 65.6 1.0 C19 A:EJP1100 3.6 66.8 1.0 N A:LEU78 3.8 70.8 1.0 C12 A:EJP1100 3.8 61.6 1.0 N2 A:EJP1100 3.9 62.1 1.0 C15 A:EJP1100 3.9 64.3 1.0 CB A:LEU78 4.1 73.2 1.0 CB A:MET67 4.2 73.8 1.0 CZ A:PHE162 4.2 75.4 1.0 CD1 A:LEU70 4.3 66.0 1.0 CG A:MET67 4.4 76.0 1.0 C A:VAL76 4.4 67.8 1.0 C A:MET67 4.4 74.7 1.0 C A:LYS77 4.5 70.6 1.0 CA A:LEU78 4.5 71.9 1.0 CA A:LYS77 4.6 70.0 1.0 C3 A:EJP1100 4.7 62.2 1.0 SD A:MET67 4.8 81.0 1.0 CA A:MET67 4.8 74.6 1.0 CB A:LEU70 4.8 69.1 1.0 C20 A:EJP1100 4.9 68.0 1.0 CE1 A:PHE162 4.9 72.9 1.0 N A:LYS77 5.0 67.1 1.0

Chlorine binding site 2 out of 4 in the Structure Based Design of RIP1 Kinase Inhibitors


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 of RIP1 Kinase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl1100 b:55.3 occ:1.00 CL1 B:EJP1100 0.0 55.3 1.0 C16 B:EJP1100 1.7 50.4 1.0 N3 B:EJP1100 2.7 48.5 1.0 C11 B:EJP1100 2.8 50.1 1.0 C24 B:EJP1100 3.1 48.1 1.0 O B:VAL76 3.3 46.1 1.0 C19 B:EJP1100 3.6 49.2 1.0 O B:MET67 3.8 58.7 1.0 C6 B:EJP1100 3.8 48.1 1.0 N2 B:EJP1100 3.9 46.3 1.0 C15 B:EJP1100 3.9 48.7 1.0 C12 B:EJP1100 3.9 46.9 1.0 N B:LEU78 4.1 52.2 1.0 CZ B:PHE162 4.2 49.7 1.0 CB B:LEU78 4.2 54.4 1.0 C B:VAL76 4.4 49.0 1.0 C B:MET67 4.6 52.9 1.0 CE1 B:PHE162 4.7 50.0 1.0 CB B:MET67 4.7 52.6 1.0 CA B:LEU78 4.7 53.0 1.0 C B:LYS77 4.7 51.9 1.0 CA B:LYS77 4.8 52.3 1.0 C20 B:EJP1100 4.9 49.7 1.0

Chlorine binding site 3 out of 4 in the Structure Based Design of RIP1 Kinase Inhibitors


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of Structure Based Design of RIP1 Kinase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ C:Cl1100 b:58.2 occ:1.00 CL1 C:EJP1100 0.0 58.2 1.0 C16 C:EJP1100 1.7 58.2 1.0 N3 C:EJP1100 2.7 56.9 1.0 C11 C:EJP1100 2.8 58.2 1.0 C24 C:EJP1100 3.1 54.9 1.0 O C:MET67 3.4 63.2 1.0 O C:VAL76 3.5 54.5 1.0 C19 C:EJP1100 3.6 60.1 1.0 C6 C:EJP1100 3.7 55.8 1.0 CB C:MET67 3.8 66.9 1.0 N2 C:EJP1100 3.9 55.5 1.0 C15 C:EJP1100 3.9 57.5 1.0 C12 C:EJP1100 3.9 53.1 1.0 C C:MET67 4.1 67.2 1.0 CA C:MET67 4.1 67.5 1.0 CD1 C:LEU70 4.3 61.7 1.0 CG C:MET67 4.4 67.5 1.0 N C:LEU78 4.4 63.8 1.0 CZ C:PHE162 4.5 62.6 1.0 CE2 C:PHE162 4.5 61.2 1.0 CB C:LEU70 4.6 62.8 1.0 CB C:LEU78 4.6 66.3 1.0 C C:VAL76 4.6 58.8 1.0 C C:LYS77 4.9 63.7 1.0 CA C:LYS77 4.9 62.0 1.0 C20 C:EJP1100 4.9 61.9 1.0 CG C:LEU70 4.9 62.4 1.0 C3 C:EJP1100 5.0 54.4 1.0

Chlorine binding site 4 out of 4 in the Structure Based Design of RIP1 Kinase Inhibitors


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 4 of Structure Based Design of RIP1 Kinase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ D:Cl1100 b:77.7 occ:1.00 CL1 D:EJP1100 0.0 77.7 1.0 C16 D:EJP1100 1.7 71.4 1.0 N3 D:EJP1100 2.7 69.2 1.0 C11 D:EJP1100 2.8 70.0 1.0 C24 D:EJP1100 3.2 68.6 1.0 O D:MET67 3.2 87.8 1.0 CG D:MET67 3.3 81.5 1.0 C19 D:EJP1100 3.6 71.2 1.0 O D:VAL76 3.8 75.6 1.0 N D:LEU78 3.9 74.2 1.0 N2 D:EJP1100 3.9 65.6 1.0 C6 D:EJP1100 3.9 71.7 1.0 C15 D:EJP1100 3.9 67.0 1.0 C D:MET67 4.0 84.2 1.0 C12 D:EJP1100 4.0 69.7 1.0 CB D:LEU78 4.1 77.6 1.0 CZ D:PHE162 4.4 79.4 1.0 CB D:MET67 4.4 82.4 1.0 CE2 D:PHE162 4.4 80.0 1.0 SD D:MET67 4.5 80.1 1.0 CA D:MET67 4.5 82.7 1.0 CA D:LEU78 4.5 75.3 1.0 C D:LYS77 4.6 73.6 1.0 C D:VAL76 4.6 73.2 1.0 CA D:LYS77 4.7 76.4 1.0 CD1 D:LEU70 4.8 80.0 1.0 CB D:LEU70 4.8 77.7 1.0 C20 D:EJP1100 4.9 71.4 1.0 N D:ASN68 5.0 85.5 1.0 N D:LYS77 5.0 74.3 1.0

M.Yoshikawa, M.Saitoh, T.Katoh, T.Seki, S.V.Bigi, Y.Shimizu, T.Ishii, T.Okai, M.Kuno, H.Hattori, E.Watanabe, K.S.Saikatendu, H.Zou, M.Nakakariya, T.Tatamiya, Y.Nakada, T.Yogo. Discovery of 7-Oxo-2,4,5,7-Tetrahydro-6 H-Pyrazolo[3,4- C]Pyridine Derivatives As Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure-Kinetic Relationships. J. Med. Chem. V. 61 2384 2018.
ISSN: ISSN 1520-4804
PubMed: 29485864
DOI: 10.1021/ACS.JMEDCHEM.7B01647