Fluorine in PDB 7ycc: Kras G12C in Complex with Compound 5C

All present enzymatic activity of Kras G12C in Complex with Compound 5C:
3.6.5.2;

The structure of Kras G12C in Complex with Compound 5C, PDB code: 7ycc was solved by Y.Amano, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	33.72 / 1.79
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	96.268, 94.407, 67.423, 90, 91.49, 90
R / Rfree (%)	21.2 / 25.5

The structure of Kras G12C in Complex with Compound 5C also contains other interesting chemical elements:

Magnesium	(Mg)	3 atoms
Chlorine	(Cl)	3 atoms

The binding sites of Fluorine atom in the Kras G12C in Complex with Compound 5C (pdb code 7ycc). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Kras G12C in Complex with Compound 5C, PDB code: 7ycc:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Kras G12C in Complex with Compound 5C


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Kras G12C in Complex with Compound 5C within 5.0Å range: probe atom residue distance (Å) B Occ A:F203 b:39.8 occ:1.00 F21 A:IQC203 0.0 39.8 1.0 C18 A:IQC203 1.3 37.9 1.0 C19 A:IQC203 2.3 38.2 1.0 C17 A:IQC203 2.3 39.7 1.0 N20 A:IQC203 2.6 35.8 1.0 C22 A:IQC203 2.8 42.9 1.0 NE2 A:HIS95 3.4 35.6 1.0 C23 A:IQC203 3.4 40.6 1.0 C27 A:IQC203 3.5 47.9 1.0 C15 A:IQC203 3.6 34.7 1.0 C13 A:IQC203 3.6 35.4 1.0 CG A:GLN99 3.6 44.1 1.0 O A:HOH365 3.6 48.1 1.0 C31 A:IQC203 3.7 38.2 1.0 CB A:GLN99 3.9 40.8 1.0 C9 A:IQC203 3.9 35.9 1.0 C28 A:IQC203 4.0 48.0 1.0 CE1 A:HIS95 4.0 34.4 1.0 C14 A:IQC203 4.1 32.7 1.0 CD2 A:HIS95 4.3 36.9 1.0 CD A:GLN99 4.4 48.3 1.0 OE1 A:GLN99 4.4 56.7 1.0 C24 A:IQC203 4.5 45.3 1.0 C26 A:IQC203 4.5 49.2 1.0 N8 A:IQC203 4.6 41.1 1.0 C11 A:IQC203 4.7 36.7 1.0 N10 A:IQC203 4.8 36.9 1.0 C25 A:IQC203 5.0 43.3 1.0

Fluorine binding site 2 out of 3 in the Kras G12C in Complex with Compound 5C


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Kras G12C in Complex with Compound 5C within 5.0Å range: probe atom residue distance (Å) B Occ B:F203 b:40.1 occ:1.00 F21 B:IQC203 0.0 40.1 1.0 C18 B:IQC203 1.3 40.3 1.0 C17 B:IQC203 2.3 42.7 1.0 C19 B:IQC203 2.3 36.4 1.0 N20 B:IQC203 2.6 37.6 1.0 C22 B:IQC203 2.8 47.6 1.0 NE2 B:HIS95 3.4 34.9 1.0 C27 B:IQC203 3.4 53.4 1.0 C23 B:IQC203 3.5 47.4 1.0 C15 B:IQC203 3.5 36.4 1.0 CG B:GLN99 3.6 43.0 1.0 C13 B:IQC203 3.6 35.4 1.0 O B:HOH375 3.7 51.1 1.0 C31 B:IQC203 3.7 44.2 1.0 CB B:GLN99 3.9 41.4 1.0 C28 B:IQC203 3.9 54.4 1.0 C9 B:IQC203 4.0 38.9 1.0 C14 B:IQC203 4.0 36.5 1.0 CE1 B:HIS95 4.1 32.1 1.0 CD2 B:HIS95 4.3 37.0 1.0 CD B:GLN99 4.5 43.4 1.0 C26 B:IQC203 4.5 54.6 1.0 C24 B:IQC203 4.5 50.5 1.0 OE1 B:GLN99 4.6 49.8 1.0 N8 B:IQC203 4.6 44.5 1.0 C11 B:IQC203 4.7 38.0 1.0 N10 B:IQC203 4.9 39.0 1.0 C25 B:IQC203 5.0 50.7 1.0

Fluorine binding site 3 out of 3 in the Kras G12C in Complex with Compound 5C


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Kras G12C in Complex with Compound 5C within 5.0Å range: probe atom residue distance (Å) B Occ C:F203 b:38.9 occ:1.00 F21 C:IQC203 0.0 38.9 1.0 C18 C:IQC203 1.3 39.5 1.0 C17 C:IQC203 2.3 42.6 1.0 C19 C:IQC203 2.4 38.4 1.0 N20 C:IQC203 2.7 40.3 1.0 C22 C:IQC203 2.8 46.6 1.0 NE2 C:HIS95 3.3 36.3 1.0 C23 C:IQC203 3.4 47.5 1.0 C27 C:IQC203 3.5 52.5 1.0 C15 C:IQC203 3.6 35.8 1.0 CG C:GLN99 3.6 39.4 1.0 C13 C:IQC203 3.6 35.5 1.0 C31 C:IQC203 3.7 41.8 1.0 CB C:GLN99 3.8 37.8 1.0 CE1 C:HIS95 3.9 33.7 1.0 C28 C:IQC203 4.0 52.7 1.0 C9 C:IQC203 4.0 39.6 1.0 C14 C:IQC203 4.1 36.9 1.0 CD2 C:HIS95 4.3 35.9 1.0 C24 C:IQC203 4.5 50.6 1.0 C26 C:IQC203 4.5 51.9 1.0 CD C:GLN99 4.6 42.4 1.0 OE1 C:GLN99 4.8 48.5 1.0 C11 C:IQC203 4.8 38.3 1.0 N8 C:IQC203 4.8 44.9 1.0 N10 C:IQC203 4.9 39.5 1.0 C25 C:IQC203 5.0 47.4 1.0

T.Imaizumi, M.Akaiwa, T.Abe, T.Nigawara, T.Koike, Y.Satake, K.Watanabe, O.Kaneko, Y.Amano, K.Mori, Y.Yamanaka, T.Nagashima, M.Shimazaki, K.Kuramoto. Discovery and Biological Evaluation of 1-{2,7-Diazaspiro[3.5]Nonan-2-Yl}Prop-2-En-1-One Derivatives As Covalent Inhibitors of Kras G12C with Favorable Metabolic Stability and Anti-Tumor Activity. Bioorg.Med.Chem. V. 71 16949 2022.
ISSN: ESSN 1464-3391
PubMed: 35926326
DOI: 10.1016/J.BMC.2022.116949