Fluorine in PDB 8pwc: Crystal Structure of MDM2 with Brigimadlin

All present enzymatic activity of Crystal Structure of MDM2 with Brigimadlin:
2.3.2.27;

The structure of Crystal Structure of MDM2 with Brigimadlin, PDB code: 8pwc was solved by G.Bader, B.Wolkerstorfer, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	41.60 / 1.46
Space group	P 32
Cell size a, b, c (Å), α, β, γ (°)	83.207, 83.207, 42.056, 90, 90, 120
R / Rfree (%)	19.9 / 22.6

The structure of Crystal Structure of MDM2 with Brigimadlin also contains other interesting chemical elements:

Chlorine

(Cl)

6 atoms

The binding sites of Fluorine atom in the Crystal Structure of MDM2 with Brigimadlin (pdb code 8pwc). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Crystal Structure of MDM2 with Brigimadlin, PDB code: 8pwc:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Crystal Structure of MDM2 with Brigimadlin


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of MDM2 with Brigimadlin within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:19.8 occ:1.00 F21 A:G7I201 0.0 19.8 1.0 C14 A:G7I201 1.3 18.2 1.0 C15 A:G7I201 2.3 18.2 1.0 H2 A:G7I201 2.4 17.3 1.0 C13 A:G7I201 2.4 16.4 1.0 HD13 A:ILE99 2.7 21.5 1.0 C2 A:G7I201 2.8 17.2 1.0 HD12 A:ILE99 2.8 21.4 1.0 CL19 A:G7I201 2.9 20.8 1.0 C6 A:G7I201 3.1 17.9 1.0 H6 A:G7I201 3.1 17.9 1.0 C7 A:G7I201 3.2 17.5 1.0 CD1 A:ILE99 3.2 21.5 1.0 HD2 A:HIS96 3.3 19.5 1.0 CD2 A:HIS96 3.4 19.5 1.0 O A:VAL93 3.5 22.6 1.0 NE2 A:HIS96 3.5 21.0 1.0 HE2 A:HIS96 3.5 21.1 1.0 C1 A:G7I201 3.5 16.8 1.0 HD22 A:LEU54 3.6 24.0 1.0 C16 A:G7I201 3.6 16.4 1.0 C18 A:G7I201 3.6 16.5 1.0 HG21 A:ILE99 3.6 20.9 1.0 C3 A:G7I201 3.6 17.9 1.0 HA A:HIS96 3.8 18.9 1.0 HD11 A:ILE99 3.8 21.5 1.0 C8 A:G7I201 3.9 17.8 1.0 HA A:VAL93 4.0 20.0 1.0 C17 A:G7I201 4.1 16.9 1.0 CG A:HIS96 4.1 18.9 1.0 HB A:ILE99 4.1 20.0 1.0 H3 A:G7I201 4.1 18.0 1.0 C24 A:G7I201 4.2 17.4 1.0 C4 A:G7I201 4.2 18.8 1.0 CE1 A:HIS96 4.3 20.8 1.0 HB A:VAL93 4.3 21.4 1.0 C5 A:G7I201 4.4 17.6 1.0 CG1 A:ILE99 4.4 20.1 1.0 C A:VAL93 4.4 21.3 1.0 C10 A:G7I201 4.4 16.8 1.0 CG2 A:ILE99 4.5 20.9 1.0 H16 A:G7I201 4.5 16.4 1.0 N9 A:G7I201 4.5 17.4 1.0 H18 A:G7I201 4.5 16.5 1.0 CD2 A:LEU54 4.5 24.0 1.0 HD21 A:LEU54 4.5 24.0 1.0 CB A:ILE99 4.6 20.1 1.0 N27 A:G7I201 4.6 18.9 1.0 ND1 A:HIS96 4.6 21.0 1.0 N20 A:G7I201 4.6 17.6 1.0 CA A:VAL93 4.7 19.9 1.0 CA A:HIS96 4.7 19.0 1.0 N29 A:G7I201 4.7 18.8 1.0 HG22 A:ILE99 4.7 20.8 1.0 H24 A:G7I201 4.8 17.4 1.0 CB A:HIS96 4.8 19.1 1.0 HB3 A:HIS96 4.9 19.0 1.0 HD13 A:LEU54 4.9 28.5 1.0 HE1 A:HIS96 4.9 20.8 1.0 HG12 A:ILE99 5.0 20.1 1.0

Fluorine binding site 2 out of 3 in the Crystal Structure of MDM2 with Brigimadlin


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of MDM2 with Brigimadlin within 5.0Å range: probe atom residue distance (Å) B Occ B:F201 b:21.1 occ:1.00 F21 B:G7I201 0.0 21.1 1.0 C14 B:G7I201 1.4 20.5 1.0 C15 B:G7I201 2.3 20.5 1.0 C13 B:G7I201 2.4 17.7 1.0 H2 B:G7I201 2.4 17.4 1.0 HD12 B:ILE99 2.6 22.7 1.0 HD13 B:ILE99 2.7 22.7 1.0 C2 B:G7I201 2.8 17.5 1.0 CL19 B:G7I201 2.9 22.9 1.0 C6 B:G7I201 3.0 19.1 1.0 H6 B:G7I201 3.1 19.1 1.0 CD1 B:ILE99 3.1 22.8 1.0 C7 B:G7I201 3.2 17.9 1.0 HD2 B:HIS96 3.4 19.8 1.0 CD2 B:HIS96 3.4 19.8 1.0 HG21 B:ILE99 3.5 22.0 1.0 HE2 B:HIS96 3.5 20.0 1.0 O B:VAL93 3.5 25.7 1.0 C1 B:G7I201 3.5 18.0 1.0 NE2 B:HIS96 3.6 19.9 1.0 C16 B:G7I201 3.6 19.6 1.0 C18 B:G7I201 3.6 17.4 1.0 C3 B:G7I201 3.6 19.5 1.0 HD22 B:LEU54 3.6 21.8 1.0 HD11 B:ILE99 3.7 22.8 1.0 HA B:HIS96 3.8 20.7 1.0 C8 B:G7I201 3.9 17.7 1.0 HA B:VAL93 4.0 22.9 1.0 H3 B:G7I201 4.0 19.6 1.0 HB B:ILE99 4.0 21.2 1.0 C17 B:G7I201 4.1 18.3 1.0 CG B:HIS96 4.1 19.8 1.0 C24 B:G7I201 4.2 18.4 1.0 C4 B:G7I201 4.2 19.5 1.0 CG1 B:ILE99 4.3 22.2 1.0 CE1 B:HIS96 4.3 20.9 1.0 HB B:VAL93 4.3 23.3 1.0 C5 B:G7I201 4.4 18.3 1.0 CG2 B:ILE99 4.4 22.0 1.0 CB B:ILE99 4.5 21.3 1.0 C10 B:G7I201 4.5 17.7 1.0 H16 B:G7I201 4.5 19.6 1.0 C B:VAL93 4.5 23.9 1.0 H18 B:G7I201 4.5 17.4 1.0 N9 B:G7I201 4.5 17.2 1.0 N27 B:G7I201 4.6 19.1 1.0 ND1 B:HIS96 4.6 21.7 1.0 N20 B:G7I201 4.6 19.0 1.0 CD2 B:LEU54 4.6 21.8 1.0 HD21 B:LEU54 4.7 21.9 1.0 CA B:VAL93 4.7 22.8 1.0 N29 B:G7I201 4.7 20.2 1.0 CA B:HIS96 4.7 20.7 1.0 HG22 B:ILE99 4.8 21.9 1.0 H24 B:G7I201 4.8 18.5 1.0 HG12 B:ILE99 4.8 22.2 1.0 CB B:HIS96 4.8 21.3 1.0 HB3 B:HIS96 4.9 21.3 1.0 HE1 B:HIS96 5.0 20.9 1.0 HD13 B:LEU54 5.0 26.3 1.0

Fluorine binding site 3 out of 3 in the Crystal Structure of MDM2 with Brigimadlin


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of MDM2 with Brigimadlin within 5.0Å range: probe atom residue distance (Å) B Occ C:F201 b:43.6 occ:0.86 F21 C:G7I201 0.0 43.6 0.9 C14 C:G7I201 1.3 44.4 0.9 C15 C:G7I201 2.3 45.0 0.9 C13 C:G7I201 2.4 44.7 0.9 H2 C:G7I201 2.4 45.1 0.9 HD12 C:ILE99 2.7 56.8 1.0 HD13 C:ILE99 2.8 56.8 1.0 C2 C:G7I201 2.8 45.1 0.9 CL19 C:G7I201 2.9 46.1 0.9 C6 C:G7I201 3.0 44.2 0.9 H6 C:G7I201 3.1 44.2 0.9 C7 C:G7I201 3.2 44.2 0.9 CD1 C:ILE99 3.2 56.8 1.0 HD2 C:HIS96 3.3 52.2 1.0 CD2 C:HIS96 3.4 52.2 1.0 HD22 C:LEU54 3.5 52.5 1.0 NE2 C:HIS96 3.5 52.8 1.0 C1 C:G7I201 3.5 44.7 0.9 HE2 C:HIS96 3.6 52.8 1.0 C3 C:G7I201 3.6 44.1 0.9 HG21 C:ILE99 3.6 55.9 1.0 O C:VAL93 3.6 59.6 1.0 C18 C:G7I201 3.6 44.5 0.9 C16 C:G7I201 3.6 44.7 0.9 HA C:HIS96 3.8 53.6 1.0 C8 C:G7I201 3.8 43.9 0.9 HD11 C:ILE99 3.9 56.8 1.0 CG C:HIS96 4.0 51.7 1.0 H3 C:G7I201 4.0 44.1 0.9 HB C:ILE99 4.1 55.5 1.0 C17 C:G7I201 4.1 44.2 0.9 HA C:VAL93 4.1 59.1 1.0 C4 C:G7I201 4.1 43.8 0.9 CE1 C:HIS96 4.2 52.8 1.0 C24 C:G7I201 4.2 45.7 0.9 C5 C:G7I201 4.3 43.7 0.9 HB C:VAL93 4.3 60.0 1.0 CG1 C:ILE99 4.4 56.0 1.0 CG2 C:ILE99 4.4 55.9 1.0 CD2 C:LEU54 4.4 52.5 1.0 HD21 C:LEU54 4.4 52.5 1.0 C10 C:G7I201 4.4 43.3 0.9 H16 C:G7I201 4.5 44.7 0.9 N9 C:G7I201 4.5 43.7 0.9 ND1 C:HIS96 4.5 52.2 1.0 CB C:ILE99 4.5 55.5 1.0 H18 C:G7I201 4.5 44.5 0.9 C C:VAL93 4.5 59.0 1.0 N27 C:G7I201 4.6 45.9 0.9 N20 C:G7I201 4.6 45.5 0.9 HG22 C:ILE99 4.7 55.9 1.0 CA C:HIS96 4.7 53.6 1.0 N29 C:G7I201 4.8 46.4 0.9 CA C:VAL93 4.8 59.1 1.0 CB C:HIS96 4.8 52.2 1.0 H24 C:G7I201 4.9 45.7 0.9 HE1 C:HIS96 4.9 52.8 1.0 HD23 C:LEU54 4.9 52.5 1.0 HG12 C:ILE99 4.9 56.0 1.0 HB3 C:HIS96 4.9 52.2 1.0 HD13 C:LEU54 5.0 53.4 1.0

A.Gollner, D.Rudolph, U.Weyer-Czernilofsky, R.Baumgartinger, P.Jung, H.Weinstabl, J.Ramharter, R.Grempler, J.Quant, J.Rinnenthal, A.Perez Pitarch, B.Golubovic, D.Gerlach, G.Bader, K.Wetzel, S.Otto, C.Mandl, G.Boehmelt, D.B.Mcconnell, N.Kraut, P.Sini. Discovery and Characterization of Brigimadlin, A Novel and Highly Potent MDM2-P53 Antagonist Suitable For Intermittent Dose Schedules. Mol.Cancer Ther. 2024.
ISSN: ESSN 1538-8514
PubMed: 39259562
DOI: 10.1158/1535-7163.MCT-23-0783