Magnesium in PDB 8x6r: KRASG12C in Complex with Inhibitor

All present enzymatic activity of KRASG12C in Complex with Inhibitor:
3.6.5.2;

The structure of KRASG12C in Complex with Inhibitor, PDB code: 8x6r was solved by Y.Amano, Y.Tateishi, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	50.00 / 1.85
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	67.525, 94.909, 96.199, 90, 91.11, 90
R / Rfree (%)	25.3 / 29.9

The binding sites of Magnesium atom in the KRASG12C in Complex with Inhibitor (pdb code 8x6r). This binding sites where shown within 5.0 Angstroms radius around Magnesium atom.
In total 6 binding sites of Magnesium where determined in the KRASG12C in Complex with Inhibitor, PDB code: 8x6r:
Jump to Magnesium binding site number: 1; 2; 3; 4; 5; 6;

Magnesium binding site 1 out of 6 in the KRASG12C in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 1 of KRASG12C in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Mg202 b:30.2 occ:1.00 O A:HOH313 1.9 21.4 1.0 O A:HOH309 1.9 22.7 1.0 O A:HOH326 2.1 29.1 1.0 O A:HOH304 2.1 21.6 1.0 O2B A:GDP201 2.2 25.6 1.0 OG A:SER17 2.2 19.4 1.0 CB A:SER17 3.3 22.4 1.0 PB A:GDP201 3.4 25.5 1.0 O1B A:GDP201 3.7 22.8 1.0 O1A A:GDP201 4.0 27.3 1.0 N A:SER17 4.1 26.2 1.0 OD2 A:ASP57 4.1 26.8 1.0 OD1 A:ASP57 4.1 26.5 1.0 CA A:SER17 4.3 21.2 1.0 O44 A:Y9D203 4.3 28.5 1.0 CD2 A:TYR32 4.3 26.9 1.0 O A:ASP33 4.4 34.5 1.0 O3A A:GDP201 4.4 26.6 1.0 O A:THR58 4.4 31.8 1.0 CA A:PRO34 4.4 33.0 1.0 O3B A:GDP201 4.4 27.1 1.0 CG A:ASP57 4.5 28.1 1.0 PA A:GDP201 4.6 27.2 1.0 O A:ILE36 4.7 25.7 1.0 CE2 A:TYR32 4.8 25.2 1.0 CB A:LYS16 4.9 20.1 1.0 CE A:LYS16 5.0 22.7 1.0 O A:TYR32 5.0 26.9 1.0 NZ A:LYS16 5.0 21.8 1.0 O2A A:GDP201 5.0 23.9 1.0

Magnesium binding site 2 out of 6 in the KRASG12C in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 2 of KRASG12C in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Mg202 b:26.5 occ:1.00 O B:HOH310 2.0 32.2 1.0 OG B:SER17 2.1 22.4 1.0 O2B B:GDP201 2.2 32.2 1.0 O B:HOH303 2.2 41.2 1.0 O B:HOH312 2.2 25.8 1.0 O B:HOH329 2.3 25.8 1.0 PB B:GDP201 3.1 27.9 1.0 O3B B:GDP201 3.3 26.4 1.0 CB B:SER17 3.4 21.4 1.0 O2A B:GDP201 4.0 28.9 1.0 O44 B:Y9D203 4.0 23.7 1.0 N B:SER17 4.0 22.6 1.0 O3A B:GDP201 4.2 25.8 1.0 O1B B:GDP201 4.2 30.0 1.0 CA B:SER17 4.3 21.8 1.0 CA B:PRO34 4.3 49.6 1.0 OD2 B:ASP57 4.4 25.9 1.0 OD1 B:ASP57 4.4 27.8 1.0 O B:ASP33 4.6 48.5 1.0 PA B:GDP201 4.6 30.9 1.0 O B:TYR32 4.7 42.7 1.0 O B:THR58 4.7 36.3 1.0 NZ B:LYS16 4.7 25.0 1.0 CG B:ASP57 4.8 27.4 1.0 CD1 B:TYR32 4.9 48.3 1.0 CB B:PRO34 5.0 50.1 1.0

Magnesium binding site 3 out of 6 in the KRASG12C in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 3 of KRASG12C in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ C:Mg202 b:25.8 occ:1.00 O C:HOH322 1.9 20.3 1.0 O C:HOH308 1.9 20.7 1.0 O C:HOH328 2.0 37.2 1.0 OG C:SER17 2.0 19.0 1.0 O1B C:GDP201 2.2 26.2 1.0 O C:HOH305 2.2 29.2 1.0 CB C:SER17 3.2 24.3 1.0 PB C:GDP201 3.4 27.1 1.0 O3B C:GDP201 3.8 23.8 1.0 OD1 C:ASP57 4.0 29.2 1.0 N C:SER17 4.0 27.3 1.0 OD2 C:ASP57 4.1 28.8 1.0 O1A C:GDP201 4.1 29.1 1.0 CA C:SER17 4.2 23.0 1.0 O C:ASP33 4.3 38.8 1.0 O44 C:Y9D203 4.3 27.5 1.0 CD2 C:TYR32 4.3 28.3 1.0 O C:THR58 4.3 34.9 1.0 O3A C:GDP201 4.4 26.2 1.0 CG C:ASP57 4.4 28.8 1.0 O2B C:GDP201 4.5 27.2 1.0 CA C:PRO34 4.6 36.9 1.0 O C:ILE36 4.6 28.1 1.0 CE2 C:TYR32 4.7 29.4 1.0 PA C:GDP201 4.7 25.7 1.0 CB C:LYS16 4.9 21.2 1.0 NZ C:LYS16 5.0 24.4 1.0 CE C:LYS16 5.0 25.8 1.0

Magnesium binding site 4 out of 6 in the KRASG12C in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 4 of KRASG12C in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ D:Mg202 b:28.4 occ:1.00 OG D:SER17 2.0 25.7 1.0 O1B D:GDP201 2.1 26.6 1.0 O D:HOH315 2.1 33.2 1.0 O D:HOH302 2.1 32.9 1.0 O D:HOH301 2.3 25.3 1.0 O D:HOH326 2.4 33.5 1.0 PB D:GDP201 3.2 25.9 1.0 O3B D:GDP201 3.3 25.4 1.0 CB D:SER17 3.4 21.7 1.0 O44 D:Y9D203 4.0 26.6 1.0 N D:SER17 4.0 24.1 1.0 O1A D:GDP201 4.0 30.3 1.0 O3A D:GDP201 4.2 24.4 1.0 CA D:SER17 4.3 23.5 1.0 O2B D:GDP201 4.3 29.7 1.0 OD1 D:ASP57 4.3 24.8 1.0 OD2 D:ASP57 4.3 28.1 1.0 CA D:PRO34 4.4 45.2 1.0 O D:THR58 4.5 35.8 1.0 PA D:GDP201 4.6 30.3 1.0 O D:ASP33 4.7 42.0 1.0 O D:TYR32 4.7 39.1 1.0 CG D:ASP57 4.7 26.5 1.0 CD2 D:TYR32 4.8 48.9 1.0 CE D:LYS16 4.8 28.9 1.0 NZ D:LYS16 5.0 27.7 1.0 CB D:LYS16 5.0 25.2 1.0

Magnesium binding site 5 out of 6 in the KRASG12C in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 5 of KRASG12C in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ E:Mg202 b:24.5 occ:1.00 O E:HOH319 1.8 20.9 1.0 O E:HOH339 2.0 33.0 1.0 O E:HOH315 2.0 17.9 1.0 OG E:SER17 2.1 20.5 1.0 O E:HOH306 2.2 26.2 1.0 O2B E:GDP201 2.2 27.0 1.0 CB E:SER17 3.2 24.2 1.0 PB E:GDP201 3.4 28.2 1.0 O1B E:GDP201 3.9 25.4 1.0 N E:SER17 4.0 26.6 1.0 OD1 E:ASP57 4.0 24.9 1.0 OD2 E:ASP57 4.1 23.6 1.0 O1A E:GDP201 4.1 25.2 1.0 CA E:SER17 4.2 22.3 1.0 CD2 E:TYR32 4.2 27.9 1.0 O44 E:Y9D203 4.3 26.2 1.0 O E:ASP33 4.4 33.6 1.0 CG E:ASP57 4.4 24.1 1.0 O3B E:GDP201 4.4 28.3 1.0 O3A E:GDP201 4.4 27.5 1.0 O E:THR58 4.4 29.6 1.0 CA E:PRO34 4.5 31.8 1.0 O E:ILE36 4.6 22.2 1.0 CE2 E:TYR32 4.6 27.3 1.0 PA E:GDP201 4.7 26.9 1.0 CB E:LYS16 4.9 20.3 1.0 NZ E:LYS16 4.9 20.7 1.0

Magnesium binding site 6 out of 6 in the KRASG12C in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 6 of KRASG12C in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ F:Mg202 b:23.7 occ:1.00 O F:HOH318 1.9 31.6 1.0 OG F:SER17 2.0 24.1 1.0 O1B F:GDP201 2.0 27.1 1.0 O F:HOH310 2.2 22.7 1.0 O F:HOH309 2.2 27.7 1.0 O F:HOH304 2.2 29.9 1.0 PB F:GDP201 3.2 26.3 1.0 CB F:SER17 3.3 23.4 1.0 O3B F:GDP201 3.5 25.2 1.0 O44 F:Y9D203 4.0 22.1 1.0 N F:SER17 4.0 23.7 1.0 O1A F:GDP201 4.1 28.0 1.0 CA F:SER17 4.2 22.9 1.0 OD1 F:ASP57 4.2 24.3 1.0 O2B F:GDP201 4.3 29.0 1.0 O3A F:GDP201 4.3 25.1 1.0 OD2 F:ASP57 4.3 26.2 1.0 CA F:PRO34 4.4 44.2 1.0 O F:ASP33 4.6 41.8 1.0 O F:ILE36 4.6 33.9 1.0 CG F:ASP57 4.7 25.1 1.0 PA F:GDP201 4.7 30.2 1.0 O F:THR58 4.7 31.1 1.0 O F:TYR32 4.8 40.0 1.0 CE F:LYS16 4.9 25.4 1.0 CD1 F:TYR32 5.0 44.3 1.0 NZ F:LYS16 5.0 26.5 1.0

T.Imaizumi, I.Shimada, Y.Satake, S.Yamaki, T.Koike, T.Nigawara, O.Kaneko, Y.Amano, K.Mori, Y.Yamanaka, A.Nakayama, Y.Nishizono, M.Shimazaki, T.Nagashima, K.Kuramoto. Discovery of ASP6918, A Kras G12C Inhibitor: Synthesis and Structure-Activity Relationships of 1-{2,7-Diazaspiro[3.5]Non-2-Yl}Prop-2-En-1-One Derivatives As Covalent Inhibitors with Good Potency and Oral Activity For the Treatment of Solid Tumors. Bioorg.Med.Chem. V. 98 17581 2023.
ISSN: ESSN 1464-3391
PubMed: 38176113
DOI: 10.1016/J.BMC.2023.117581