Fluorine in PDB 5lay: Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G

The structure of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G, PDB code: 5lay was solved by D.Kessler, A.Gollner, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	87.45 / 2.71
Space group	P 65 2 2
Cell size a, b, c (Å), α, β, γ (°)	71.450, 71.450, 520.977, 90.00, 90.00, 120.00
R / Rfree (%)	25.1 / 29.2

The structure of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G also contains other interesting chemical elements:

Chlorine

(Cl)

12 atoms

The binding sites of Fluorine atom in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G (pdb code 5lay). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G, PDB code: 5lay:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G within 5.0Å range: probe atom residue distance (Å) B Occ A:F205 b:7.8 occ:1.00 F38 A:6SS205 0.0 7.8 1.0 C37 A:6SS205 1.4 7.8 1.0 C2 A:6SS205 2.4 7.7 1.0 C6 A:6SS205 2.4 7.6 1.0 C7 A:6SS205 2.8 7.3 1.0 CL1 A:6SS205 2.9 8.1 1.0 C28 A:6SS205 3.0 7.3 1.0 C27 A:6SS205 3.2 7.2 1.0 CD1 A:ILE99 3.4 6.9 1.0 O A:VAL93 3.6 8.1 1.0 C26 A:6SS205 3.6 7.2 1.0 C3 A:6SS205 3.6 7.4 1.0 C29 A:6SS205 3.6 7.1 1.0 C5 A:6SS205 3.7 7.9 1.0 CD2 A:HIS96 3.8 13.2 1.0 NE2 A:HIS96 3.8 13.7 1.0 C33 A:6SS205 3.9 7.1 1.0 C4 A:6SS205 4.1 7.6 1.0 C9 A:6SS205 4.3 7.3 1.0 C30 A:6SS205 4.3 7.1 1.0 C32 A:6SS205 4.4 7.0 1.0 CE1 A:HIS96 4.4 13.9 1.0 CD1 A:LEU54 4.4 6.5 1.0 CG A:HIS96 4.5 13.2 1.0 C35 A:6SS205 4.5 7.1 1.0 C A:VAL93 4.5 7.7 1.0 CG2 A:ILE99 4.5 6.9 1.0 N34 A:6SS205 4.6 7.2 1.0 N15 A:6SS205 4.6 7.1 1.0 N11 A:6SS205 4.6 7.4 1.0 CG1 A:ILE99 4.6 6.9 1.0 CA A:VAL93 4.7 7.2 1.0 CB A:VAL93 4.8 7.1 1.0 ND1 A:HIS96 4.8 13.6 1.0 CB A:ILE99 4.8 6.9 1.0

Fluorine binding site 2 out of 6 in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G within 5.0Å range: probe atom residue distance (Å) B Occ B:F202 b:7.6 occ:1.00 F38 B:6SS202 0.0 7.6 1.0 C37 B:6SS202 1.4 7.5 1.0 C2 B:6SS202 2.3 7.7 1.0 C6 B:6SS202 2.4 6.9 1.0 C7 B:6SS202 2.8 6.4 1.0 CL1 B:6SS202 2.9 8.9 1.0 C28 B:6SS202 3.0 6.7 1.0 C27 B:6SS202 3.2 6.7 1.0 CD1 B:ILE99 3.3 4.4 1.0 C26 B:6SS202 3.6 6.3 1.0 C3 B:6SS202 3.6 7.3 1.0 CD2 B:HIS96 3.6 10.1 1.0 C5 B:6SS202 3.7 7.0 1.0 O B:VAL93 3.7 3.8 1.0 C29 B:6SS202 3.7 6.7 1.0 C33 B:6SS202 4.0 6.9 1.0 C4 B:6SS202 4.1 7.1 1.0 C9 B:6SS202 4.3 5.9 1.0 NE2 B:HIS96 4.3 10.2 1.0 CD1 B:LEU54 4.4 5.5 1.0 C30 B:6SS202 4.5 7.0 1.0 CG2 B:ILE99 4.5 4.3 1.0 N11 B:6SS202 4.5 5.6 1.0 CG1 B:ILE99 4.5 4.3 1.0 C35 B:6SS202 4.6 6.3 1.0 N15 B:6SS202 4.6 6.0 1.0 C32 B:6SS202 4.6 6.9 1.0 C B:VAL93 4.6 3.5 1.0 CB B:ILE99 4.7 4.5 1.0 N34 B:6SS202 4.7 6.6 1.0 CG B:HIS96 4.8 9.7 1.0 CA B:VAL93 4.9 3.3 1.0

Fluorine binding site 3 out of 6 in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G within 5.0Å range: probe atom residue distance (Å) B Occ C:F202 b:8.0 occ:1.00 F38 C:6SS202 0.0 8.0 1.0 C37 C:6SS202 1.4 8.2 1.0 C2 C:6SS202 2.3 8.2 1.0 C6 C:6SS202 2.4 7.9 1.0 C7 C:6SS202 2.8 7.6 1.0 CL1 C:6SS202 2.8 8.7 1.0 C28 C:6SS202 3.0 6.8 1.0 C27 C:6SS202 3.2 7.0 1.0 CD1 C:ILE99 3.3 5.9 1.0 O C:VAL93 3.5 6.0 1.0 C26 C:6SS202 3.6 7.3 1.0 C3 C:6SS202 3.6 8.2 1.0 C5 C:6SS202 3.7 8.1 1.0 C29 C:6SS202 3.7 6.6 1.0 C33 C:6SS202 4.0 7.0 1.0 ND1 C:HIS96 4.1 9.3 1.0 C4 C:6SS202 4.1 8.1 1.0 CE1 C:HIS96 4.1 9.4 1.0 O C:HOH307 4.2 30.9 1.0 C9 C:6SS202 4.3 7.7 1.0 C30 C:6SS202 4.4 6.6 1.0 C32 C:6SS202 4.5 6.8 1.0 C C:VAL93 4.5 6.0 1.0 CD1 C:LEU54 4.5 5.4 1.0 C35 C:6SS202 4.5 7.2 1.0 CG2 C:ILE99 4.5 5.9 1.0 N11 C:6SS202 4.6 8.3 1.0 CG1 C:ILE99 4.6 5.9 1.0 N15 C:6SS202 4.6 7.6 1.0 N34 C:6SS202 4.6 7.0 1.0 CA C:VAL93 4.7 5.8 1.0 CB C:VAL93 4.8 5.5 1.0 CB C:ILE99 4.8 5.9 1.0 CG C:HIS96 4.9 8.7 1.0

Fluorine binding site 4 out of 6 in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G within 5.0Å range: probe atom residue distance (Å) B Occ D:F202 b:6.0 occ:1.00 F38 D:6SS202 0.0 6.0 1.0 C37 D:6SS202 1.4 6.0 1.0 C2 D:6SS202 2.4 6.3 1.0 C6 D:6SS202 2.4 5.6 1.0 C7 D:6SS202 2.9 5.0 1.0 CL1 D:6SS202 2.9 7.0 1.0 C28 D:6SS202 3.1 5.8 1.0 C27 D:6SS202 3.2 5.4 1.0 CD1 D:ILE99 3.3 7.7 1.0 C26 D:6SS202 3.6 5.0 1.0 C3 D:6SS202 3.6 6.2 1.0 C5 D:6SS202 3.7 5.9 1.0 O D:VAL93 3.7 6.6 1.0 C29 D:6SS202 3.7 5.9 1.0 C33 D:6SS202 3.9 5.5 1.0 NE2 D:HIS96 4.0 13.1 1.0 C4 D:6SS202 4.1 6.1 1.0 CD2 D:HIS96 4.2 13.0 1.0 C9 D:6SS202 4.3 4.7 1.0 CE1 D:HIS96 4.3 13.4 1.0 C30 D:6SS202 4.3 6.1 1.0 C32 D:6SS202 4.5 5.8 1.0 CG1 D:ILE99 4.5 7.8 1.0 CG2 D:ILE99 4.5 7.6 1.0 CG D:HIS96 4.5 12.8 1.0 C35 D:6SS202 4.6 5.2 1.0 ND1 D:HIS96 4.6 13.8 1.0 N34 D:6SS202 4.6 5.4 1.0 C D:VAL93 4.6 6.0 1.0 N11 D:6SS202 4.6 4.5 1.0 N15 D:6SS202 4.7 4.5 1.0 CB D:ILE99 4.8 7.9 1.0 CA D:VAL93 4.8 5.7 1.0 CB D:VAL93 4.9 5.6 1.0 CD2 D:LEU54 4.9 3.7 1.0

Fluorine binding site 5 out of 6 in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G within 5.0Å range: probe atom residue distance (Å) B Occ E:F203 b:5.0 occ:1.00 F38 E:6SS203 0.0 5.0 1.0 C37 E:6SS203 1.4 5.1 1.0 C2 E:6SS203 2.4 5.2 1.0 C6 E:6SS203 2.4 4.9 1.0 C7 E:6SS203 2.8 4.9 1.0 CL1 E:6SS203 2.9 5.5 1.0 C28 E:6SS203 3.1 4.2 1.0 CD1 E:ILE99 3.2 6.6 1.0 C27 E:6SS203 3.3 4.3 1.0 ND1 E:HIS96 3.6 9.5 1.0 C3 E:6SS203 3.6 5.2 1.0 C5 E:6SS203 3.7 4.9 1.0 C26 E:6SS203 3.7 4.5 1.0 O E:VAL93 3.7 7.0 1.0 C29 E:6SS203 3.8 4.0 1.0 CE1 E:HIS96 3.9 9.8 1.0 C33 E:6SS203 4.1 4.2 1.0 C4 E:6SS203 4.1 5.0 1.0 C9 E:6SS203 4.2 5.2 1.0 N11 E:6SS203 4.4 5.3 1.0 CG2 E:ILE99 4.4 6.8 1.0 CG1 E:ILE99 4.5 6.7 1.0 CD1 E:LEU54 4.5 2.0 1.0 C30 E:6SS203 4.5 4.0 1.0 CB E:ILE99 4.6 6.9 1.0 C35 E:6SS203 4.6 4.4 1.0 N15 E:6SS203 4.7 4.7 1.0 C32 E:6SS203 4.7 4.0 1.0 CG E:HIS96 4.7 9.5 1.0 C E:VAL93 4.8 6.7 1.0 N34 E:6SS203 4.8 4.2 1.0

Fluorine binding site 6 out of 6 in the Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Discovery of New Natural-Product-Inspired Spiro-Oxindole Compounds As Orally Active Inhibitors of the MDM2-P53 Interaction: HDM2 (MDM2) in Complex with Compound 6G within 5.0Å range: probe atom residue distance (Å) B Occ F:F201 b:12.7 occ:1.00 F38 F:6SS201 0.0 12.7 1.0 C37 F:6SS201 1.4 12.8 1.0 C2 F:6SS201 2.3 12.7 1.0 C6 F:6SS201 2.4 12.8 1.0 C7 F:6SS201 2.9 12.8 1.0 CL1 F:6SS201 2.9 12.4 1.0 C28 F:6SS201 2.9 12.7 1.0 C27 F:6SS201 3.2 12.7 1.0 C29 F:6SS201 3.5 12.5 1.0 C3 F:6SS201 3.6 12.6 1.0 C26 F:6SS201 3.6 12.8 1.0 C5 F:6SS201 3.7 12.7 1.0 CD1 F:ILE99 3.8 7.7 1.0 C33 F:6SS201 4.0 12.6 1.0 C4 F:6SS201 4.1 12.5 1.0 C30 F:6SS201 4.2 12.1 1.0 C9 F:6SS201 4.3 12.8 1.0 C32 F:6SS201 4.4 12.1 1.0 N11 F:6SS201 4.6 12.9 1.0 NE2 F:HIS96 4.6 8.7 1.0 C35 F:6SS201 4.6 13.1 1.0 N15 F:6SS201 4.6 12.6 1.0 N34 F:6SS201 4.7 13.0 1.0 CD2 F:HIS96 4.8 8.7 1.0 CE1 F:HIS96 4.8 8.6 1.0 CG2 F:ILE99 5.0 8.0 1.0

A.Gollner, D.Rudolph, H.Arnhof, M.Bauer, S.M.Blake, G.Boehmelt, X.L.Cockroft, G.Dahmann, P.Ettmayer, T.Gerstberger, J.Karolyi-Oezguer, D.Kessler, C.Kofink, J.Ramharter, J.Rinnenthal, A.Savchenko, R.Schnitzer, H.Weinstabl, U.Weyer-Czernilofsky, T.Wunberg, D.B.Mcconnell. Discovery of Novel Spiro[3H-Indole-3,2'-Pyrrolidin]-2(1H)-One Compounds As Chemically Stable and Orally Active Inhibitors of the MDM2-P53 Interaction. J. Med. Chem. V. 59 10147 2016.
ISSN: ISSN 1520-4804
PubMed: 27775892
DOI: 10.1021/ACS.JMEDCHEM.6B00900