Fluorine in PDB 7t47: Kras G12D (Gppcp) with Mrtx-1133

All present enzymatic activity of Kras G12D (Gppcp) with Mrtx-1133:
3.6.5.2;

The structure of Kras G12D (Gppcp) with Mrtx-1133, PDB code: 7t47 was solved by N.C.Thomas, R.J.Gunn, J.D.Lawson, X.Wang, M.A.Matthew, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	46.45 / 1.27
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	40.311, 50.579, 92.903, 90, 90, 90
R / Rfree (%)	15.2 / 17.2

The structure of Kras G12D (Gppcp) with Mrtx-1133 also contains other interesting chemical elements:

Magnesium

(Mg)

1 atom

The binding sites of Fluorine atom in the Kras G12D (Gppcp) with Mrtx-1133 (pdb code 7t47). 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 G12D (Gppcp) with Mrtx-1133, PDB code: 7t47:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Kras G12D (Gppcp) with Mrtx-1133


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Kras G12D (Gppcp) with Mrtx-1133 within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:10.5 occ:1.00 F01 A:6IC201 0.0 10.5 1.0 C07 A:6IC201 1.4 9.9 1.0 C02 A:6IC201 2.3 10.1 1.0 C06 A:6IC201 2.5 10.7 1.0 N01 A:6IC201 2.7 9.8 1.0 C08 A:6IC201 2.9 10.6 1.0 C20 A:6IC201 3.2 10.3 1.0 NE2 A:HIS95 3.3 10.6 1.0 OH A:TYR64 3.3 11.9 1.0 CE2 A:TYR64 3.3 11.6 1.0 C24 A:6IC201 3.3 9.8 1.0 C32 A:6IC201 3.3 9.6 1.0 CG A:GLN99 3.5 9.9 1.0 C01 A:6IC201 3.6 9.8 1.0 N03 A:6IC201 3.7 10.5 1.0 CZ A:TYR64 3.7 10.5 1.0 C33 A:6IC201 3.8 10.6 1.0 C16 A:6IC201 3.8 12.1 1.0 CD A:GLN99 4.0 12.6 1.0 CE1 A:HIS95 4.0 10.0 1.0 CB A:GLN99 4.0 9.6 1.0 C03 A:6IC201 4.0 9.7 1.0 CD2 A:HIS95 4.1 9.3 1.0 C05 A:6IC201 4.1 10.9 1.0 C19 A:6IC201 4.2 9.3 1.0 C23 A:6IC201 4.2 8.5 1.0 CE1 A:TYR96 4.3 9.4 1.0 OE1 A:GLN99 4.3 15.1 1.0 CD1 A:TYR96 4.3 9.3 1.0 CD2 A:TYR64 4.4 11.1 1.0 NE2 A:GLN99 4.6 12.9 1.0 C17 A:6IC201 4.7 11.4 1.0 C04 A:6IC201 4.7 10.9 1.0 C18 A:6IC201 4.8 10.0 1.0 O01 A:6IC201 4.8 10.4 1.0 N02 A:6IC201 4.9 10.1 1.0 F23 A:6IC201 4.9 10.4 1.0 C21 A:6IC201 5.0 10.0 1.0

Fluorine binding site 2 out of 3 in the Kras G12D (Gppcp) with Mrtx-1133


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Kras G12D (Gppcp) with Mrtx-1133 within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:15.4 occ:1.00 F02 A:6IC201 0.0 15.4 1.0 C27 A:6IC201 1.4 11.8 1.0 C28 A:6IC201 2.3 13.9 1.0 C26 A:6IC201 2.4 12.3 1.0 N06 A:6IC201 2.9 12.3 1.0 C25 A:6IC201 3.0 11.4 1.0 C29 A:6IC201 3.2 15.9 1.0 O A:HOH512 3.2 22.8 1.0 O A:HOH398 3.2 23.6 1.0 C31 A:6IC201 3.3 14.7 1.0 OD1 A:ASP92 3.8 13.2 1.0 C30 A:6IC201 3.9 16.9 1.0 NZ A:LYS88 4.0 18.0 1.0 O A:HOH350 4.1 22.6 1.0 CG A:ASP92 4.4 13.2 1.0 C09 A:6IC201 4.5 11.8 1.0 OD2 A:ASP92 4.8 14.7 1.0 O01 A:6IC201 4.9 10.4 1.0 CG A:HIS95 4.9 8.6 1.0 CB A:HIS95 5.0 9.4 1.0

Fluorine binding site 3 out of 3 in the Kras G12D (Gppcp) with Mrtx-1133


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Kras G12D (Gppcp) with Mrtx-1133 within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:10.4 occ:1.00 F23 A:6IC201 0.0 10.4 1.0 C23 A:6IC201 1.4 8.5 1.0 C22 A:6IC201 2.3 9.6 1.0 C24 A:6IC201 2.3 9.8 1.0 C32 A:6IC201 2.7 9.6 1.0 C33 A:6IC201 3.4 10.6 1.0 CG1 A:VAL9 3.4 9.1 1.0 CG1 A:ILE100 3.5 9.8 1.0 C21 A:6IC201 3.5 10.0 1.0 C20 A:6IC201 3.6 10.3 1.0 CD1 A:ILE100 4.0 10.0 1.0 CB A:VAL9 4.0 7.3 1.0 C19 A:6IC201 4.1 9.3 1.0 O A:TYR96 4.2 8.6 1.0 CG2 A:VAL9 4.2 9.3 1.0 CD1 A:TYR96 4.4 9.3 1.0 SD A:MET72 4.5 16.0 1.0 CD2 A:PHE78 4.5 9.9 1.0 CE2 A:PHE78 4.6 11.5 1.0 CB A:GLN99 4.6 9.6 1.0 N A:ILE100 4.7 9.2 1.0 CB A:TYR96 4.8 9.2 1.0 CB A:ILE100 4.8 9.6 1.0 C08 A:6IC201 4.8 10.6 1.0 CE A:MET72 4.9 18.7 1.0 CA A:TYR96 4.9 8.6 1.0 C A:TYR96 4.9 10.0 1.0 F01 A:6IC201 4.9 10.5 1.0 CA A:ILE100 5.0 9.7 1.0

J.Christensen, J.Hallin, V.Bowcut, A.Calinsan, D.Briere, L.Hargis, L.Engstrom, J.Laguer, J.Medwid, D.Vanderpool, E.Lifset, D.Trinh, N.Hoffman, X.Wang, J.Lawson, R.Gunn, C.Smith, N.Thomas, M.Martinson, A.Bergstrom, F.Sullivan, K.Bouhana, S.Winski, L.He, F.B.Julio, A.Pavlicek, J.Hafing, L.Rahbaek, M.Marx, P.Olson. A Non-Covalent KRASG12D Allele Specific Inhibitor Demonstrates Potent Inhibition of Kras-Dependent Signaling and Regression of KRASG12D-Mutant Tumors Nature 2022.
ISSN: ESSN 1476-4687
DOI: 10.21203/RS.3.RS-1261963/V1