Fluorine in PDB 4jvr: Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide

The structure of Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide, PDB code: 4jvr was solved by X.Huang, F.Gonzalez-Lopez De Turiso, D.Sun, R.Yosup, M.D.Bartberger, H.P.Beck, J.Cannon, P.Shaffer, J.D.Oliner, S.H.Olson, J.C.Medina, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	30.00 / 1.70
Space group	C 2 2 21
Cell size a, b, c (Å), α, β, γ (°)	56.678, 98.376, 104.574, 90.00, 90.00, 90.00
R / Rfree (%)	25.6 / 27

The structure of Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide also contains other interesting chemical elements:

Chlorine

(Cl)

6 atoms

The binding sites of Fluorine atom in the Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide (pdb code 4jvr). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide, PDB code: 4jvr:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:25.8 occ:1.00 F1 A:1MT201 0.0 25.8 1.0 C2 A:1MT201 1.3 26.1 1.0 C6 A:1MT201 2.4 25.8 1.0 C1 A:1MT201 2.4 25.9 1.0 C7 A:1MT201 2.8 28.0 1.0 CL1 A:1MT201 2.9 25.9 1.0 C20 A:1MT201 3.2 22.9 1.0 NE2 A:HIS96 3.3 27.3 1.0 CD2 A:HIS96 3.3 26.7 1.0 C19 A:1MT201 3.3 24.5 1.0 CD1 A:ILE99 3.6 22.0 1.0 C5 A:1MT201 3.6 25.6 1.0 C18 A:1MT201 3.6 26.2 1.0 C3 A:1MT201 3.7 25.6 1.0 C21 A:1MT201 3.9 21.8 1.0 CE1 A:HIS96 3.9 27.6 1.0 O1 A:1MT201 4.0 34.4 1.0 CG A:HIS96 4.0 26.8 1.0 C24 A:1MT201 4.0 21.7 1.0 C4 A:1MT201 4.1 26.4 1.0 CG2 A:ILE99 4.2 20.7 1.0 C8 A:1MT201 4.2 30.5 1.0 O A:VAL93 4.2 35.0 1.0 ND1 A:HIS96 4.3 27.2 1.0 C25 A:1MT201 4.4 25.1 1.0 C15 A:1MT201 4.5 33.4 1.0 CB A:ILE99 4.5 19.8 1.0 C22 A:1MT201 4.5 21.3 1.0 CG1 A:ILE99 4.6 20.4 1.0 C23 A:1MT201 4.6 22.4 1.0 N2 A:1MT201 4.6 24.2 1.0 CD2 A:LEU54 4.8 20.0 1.0 C9 A:1MT201 4.9 28.8 1.0 CA A:HIS96 4.9 26.1 1.0 CB A:HIS96 5.0 25.4 1.0

Fluorine binding site 2 out of 3 in the Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide within 5.0Å range: probe atom residue distance (Å) B Occ C:F201 b:25.4 occ:1.00 F1 C:1MT201 0.0 25.4 1.0 C2 C:1MT201 1.3 25.2 1.0 C6 C:1MT201 2.3 26.6 1.0 C1 C:1MT201 2.4 25.6 1.0 C7 C:1MT201 2.8 28.0 1.0 CL1 C:1MT201 3.0 25.7 1.0 CD1 C:ILE99 3.1 22.0 1.0 C20 C:1MT201 3.3 22.8 1.0 C19 C:1MT201 3.4 24.1 1.0 CD2 C:HIS96 3.5 28.8 1.0 NE2 C:HIS96 3.6 29.5 1.0 C5 C:1MT201 3.6 25.1 1.0 C3 C:1MT201 3.6 24.8 1.0 C18 C:1MT201 3.7 26.3 1.0 O C:VAL93 3.9 36.2 1.0 CG C:HIS96 3.9 28.2 1.0 C21 C:1MT201 4.0 21.9 1.0 CE1 C:HIS96 4.0 29.1 1.0 O1 C:1MT201 4.0 33.4 1.0 CG2 C:ILE99 4.0 19.7 1.0 C24 C:1MT201 4.1 22.8 1.0 C4 C:1MT201 4.1 26.6 1.0 C8 C:1MT201 4.2 30.4 1.0 ND1 C:HIS96 4.2 28.5 1.0 CG1 C:ILE99 4.2 20.7 1.0 CB C:ILE99 4.3 20.2 1.0 C15 C:1MT201 4.4 32.9 1.0 C25 C:1MT201 4.5 25.4 1.0 CG2 C:VAL93 4.5 37.5 1.0 C22 C:1MT201 4.6 21.6 1.0 N2 C:1MT201 4.7 24.4 1.0 C23 C:1MT201 4.7 22.2 1.0 CB C:HIS96 4.7 25.8 1.0 CA C:HIS96 4.7 26.8 1.0 C C:VAL93 4.8 35.5 1.0 C9 C:1MT201 4.9 28.8 1.0

Fluorine binding site 3 out of 3 in the Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Co-Crystal Structure of MDM2 with Inhibitor (2'S,3R,4'S,5'R)-N-(2- Aminoethyl)-6-Chloro-4'-(3-Chloro-2-Fluorophenyl)-2'-(2,2- Dimethylpropyl)-2-Oxo-1,2-Dihydrospiro[Indole-3,3'-Pyrrolidine]-5'- Carboxamide within 5.0Å range: probe atom residue distance (Å) B Occ E:F201 b:27.4 occ:1.00 F1 E:1MT201 0.0 27.4 1.0 C2 E:1MT201 1.4 25.7 1.0 C1 E:1MT201 2.4 26.1 1.0 C6 E:1MT201 2.4 27.2 1.0 CL1 E:1MT201 2.9 25.6 1.0 C7 E:1MT201 2.9 27.8 1.0 CD2 E:HIS96 3.2 27.6 1.0 NE2 E:HIS96 3.3 27.8 1.0 C20 E:1MT201 3.3 22.1 1.0 CD1 E:ILE99 3.4 23.0 1.0 C19 E:1MT201 3.4 23.9 1.0 C5 E:1MT201 3.6 25.8 1.0 C3 E:1MT201 3.6 25.0 1.0 C18 E:1MT201 3.7 25.8 1.0 O E:VAL93 3.9 36.7 1.0 CG E:HIS96 3.9 27.2 1.0 C21 E:1MT201 4.0 21.3 1.0 CE1 E:HIS96 4.0 28.1 1.0 CG2 E:ILE99 4.0 21.6 1.0 O1 E:1MT201 4.1 34.3 1.0 C4 E:1MT201 4.1 27.8 1.0 C24 E:1MT201 4.2 22.1 1.0 C8 E:1MT201 4.2 30.2 1.0 ND1 E:HIS96 4.3 27.7 1.0 CB E:ILE99 4.4 21.0 1.0 CG1 E:ILE99 4.4 21.5 1.0 C15 E:1MT201 4.4 33.3 1.0 C25 E:1MT201 4.5 24.5 1.0 C22 E:1MT201 4.6 21.5 1.0 C23 E:1MT201 4.7 22.5 1.0 N2 E:1MT201 4.7 24.0 1.0 CB E:HIS96 4.7 25.1 1.0 CA E:HIS96 4.8 26.4 1.0 C E:VAL93 4.8 36.1 1.0 CD2 E:LEU54 4.9 20.1 1.0 C9 E:1MT201 5.0 28.0 1.0

F.Gonzalez-Lopez De Turiso, D.Sun, Y.Rew, M.D.Bartberger, H.P.Beck, J.Canon, A.Chen, D.Chow, T.L.Correll, X.Huang, L.D.Julian, F.Kayser, M.C.Lo, A.M.Long, D.Mcminn, J.D.Oliner, T.Osgood, J.P.Powers, A.Y.Saiki, S.Schneider, P.Shaffer, S.H.Xiao, P.Yakowec, X.Yan, Q.Ye, D.Yu, X.Zhao, J.Zhou, J.C.Medina, S.H.Olson. Rational Design and Binding Mode Duality of MDM2-P53 Inhibitors. J.Med.Chem. V. 56 4053 2013.
ISSN: ISSN 0022-2623
PubMed: 23597064
DOI: 10.1021/JM400293Z