Magnesium in PDB 8afd: Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A

All present enzymatic activity of Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A:
3.6.5.2;

The structure of Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A, PDB code: 8afd was solved by J.Boettcher, D.Kessler, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	32.56 / 1.63
Space group	C 2 2 21
Cell size a, b, c (Å), α, β, γ (°)	94.891, 98.614, 148.116, 90, 90, 90
R / Rfree (%)	23.1 / 26.5

The binding sites of Magnesium atom in the Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A (pdb code 8afd). This binding sites where shown within 5.0 Angstroms radius around Magnesium atom.
In total 4 binding sites of Magnesium where determined in the Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A, PDB code: 8afd:
Jump to Magnesium binding site number: 1; 2; 3; 4;

Magnesium binding site 1 out of 4 in the Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 1 of Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A within 5.0Å range: probe atom residue distance (Å) B Occ A:Mg203 b:15.4 occ:1.00 OG A:SER17 2.0 13.6 1.0 O1B A:GDP201 2.2 18.1 1.0 O A:HOH306 2.2 11.1 1.0 O A:HOH334 2.2 13.9 1.0 O A:HOH329 2.2 12.1 1.0 O A:HOH315 2.2 16.1 1.0 CB A:SER17 3.1 14.1 1.0 HB2 A:SER17 3.1 14.1 0.0 H A:SER17 3.2 13.9 0.0 PB A:GDP201 3.4 18.9 1.0 HD2 A:TYR32 3.4 37.1 0.0 HA A:PRO34 3.6 24.3 0.0 O2B A:GDP201 3.6 18.0 1.0 HB2 A:ALA59 3.7 19.6 0.0 HB3 A:SER17 3.8 14.1 0.0 N A:SER17 3.9 13.9 1.0 HB2 A:LYS16 3.9 14.3 0.0 HE2 A:TYR32 4.0 37.5 0.0 OD2 A:ASP57 4.0 18.2 1.0 CA A:SER17 4.0 14.2 1.0 OD1 A:ASP57 4.1 18.9 1.0 O1A A:GDP201 4.1 18.9 1.0 CD2 A:TYR32 4.3 37.1 1.0 HE2 A:LYS16 4.3 13.8 0.0 HA A:SER17 4.3 14.2 0.0 O3A A:GDP201 4.3 18.4 1.0 O A:PRO34 4.3 21.5 1.0 O A:ASP33 4.3 26.3 1.0 O3B A:GDP201 4.5 18.8 1.0 CG A:ASP57 4.5 17.9 1.0 O A:THR58 4.5 16.0 1.0 CE2 A:TYR32 4.5 37.5 1.0 O A:ILE36 4.5 20.4 1.0 PA A:GDP201 4.5 18.9 1.0 CA A:PRO34 4.6 24.3 1.0 O2A A:GDP201 4.6 19.2 1.0 HZ3 A:LYS16 4.6 13.0 0.0 CB A:ALA59 4.6 19.6 1.0 HB1 A:ALA59 4.7 19.6 0.0 C A:PRO34 4.7 22.8 1.0 O A:HOH349 4.8 20.8 1.0 HZ1 A:LYS16 4.9 13.0 0.0 O A:TYR32 4.9 34.4 1.0 CB A:LYS16 5.0 14.3 1.0

Magnesium binding site 2 out of 4 in the Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 2 of Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A within 5.0Å range: probe atom residue distance (Å) B Occ B:Mg202 b:28.4 occ:1.00 O B:HOH311 2.1 34.2 1.0 O1B B:GDP201 2.1 29.4 1.0 OG B:SER17 2.2 26.9 1.0 O B:HOH302 2.3 28.1 1.0 O B:HOH308 2.4 29.2 1.0 HB2 B:SER17 3.0 26.7 0.0 H B:SER17 3.1 25.4 0.0 CB B:SER17 3.1 26.7 1.0 PB B:GDP201 3.4 30.5 1.0 HD2 B:TYR32 3.5 52.5 0.0 HB2 B:ALA59 3.5 32.8 0.0 O2B B:GDP201 3.6 30.5 1.0 HA B:PRO34 3.7 45.8 0.0 HB2 B:LYS16 3.8 23.4 0.0 N B:SER17 3.8 25.4 1.0 HB3 B:SER17 3.9 26.7 0.0 CA B:SER17 4.0 26.0 1.0 HE2 B:LYS16 4.1 22.0 0.0 HE2 B:TYR32 4.1 53.5 0.0 O2A B:GDP201 4.2 30.7 1.0 OD1 B:ASP57 4.2 30.4 1.0 OD2 B:ASP57 4.3 31.9 1.0 O3A B:GDP201 4.3 30.2 1.0 HB1 B:ALA59 4.4 32.8 0.0 O B:ASP33 4.4 48.6 1.0 O B:ILE36 4.4 34.3 1.0 CB B:ALA59 4.4 32.8 1.0 O3B B:GDP201 4.4 29.6 1.0 CD2 B:TYR32 4.4 52.5 1.0 O B:PRO34 4.4 43.1 1.0 HA B:SER17 4.4 26.0 0.0 HZ3 B:LYS16 4.5 21.5 0.0 O B:THR58 4.5 25.9 1.0 PA B:GDP201 4.6 31.5 1.0 O1A B:GDP201 4.6 32.2 1.0 O B:HOH325 4.6 29.2 1.0 CG B:ASP57 4.7 30.0 1.0 CA B:PRO34 4.7 45.8 1.0 CE2 B:TYR32 4.7 53.5 1.0 HZ1 B:LYS16 4.8 21.5 0.0 C B:PRO34 4.8 44.6 1.0 CB B:LYS16 4.8 23.4 1.0 C B:LYS16 4.9 24.1 1.0 H B:LYS16 5.0 24.8 0.0 NZ B:LYS16 5.0 21.5 1.0

Magnesium binding site 3 out of 4 in the Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 3 of Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A within 5.0Å range: probe atom residue distance (Å) B Occ C:Mg202 b:13.7 occ:1.00 O C:HOH323 2.0 15.3 1.0 O1B C:GDP201 2.1 13.6 1.0 O C:HOH341 2.1 23.3 1.0 O C:HOH345 2.1 11.3 1.0 OG C:SER17 2.2 14.5 1.0 O C:HOH303 2.4 16.6 1.0 H C:SER17 3.2 14.7 0.0 HB2 C:SER17 3.2 14.8 0.0 CB C:SER17 3.3 14.8 1.0 PB C:GDP201 3.3 14.6 1.0 O2B C:GDP201 3.5 13.7 1.0 HA C:PRO34 3.6 27.2 0.0 HD2 C:TYR32 3.6 34.0 0.0 HB2 C:ALA59 3.8 24.3 0.0 HB2 C:LYS16 3.8 15.2 0.0 N C:SER17 3.9 14.7 1.0 HB3 C:SER17 4.1 14.8 0.0 HE2 C:LYS16 4.1 16.7 0.0 OD2 C:ASP57 4.1 19.1 1.0 O1A C:GDP201 4.2 15.4 1.0 CA C:SER17 4.2 14.7 1.0 HE2 C:TYR32 4.2 34.2 0.0 OD1 C:ASP57 4.2 19.5 1.0 O C:PRO34 4.3 24.4 1.0 O3A C:GDP201 4.3 14.5 1.0 O C:ASP33 4.4 29.3 1.0 O3B C:GDP201 4.4 13.4 1.0 HZ3 C:LYS16 4.5 16.9 0.0 O C:THR58 4.5 22.0 1.0 O C:ILE36 4.5 25.0 1.0 CD2 C:TYR32 4.5 34.0 1.0 CA C:PRO34 4.5 27.2 1.0 HA C:SER17 4.5 14.7 0.0 CG C:ASP57 4.6 18.8 1.0 PA C:GDP201 4.6 15.6 1.0 HZ1 C:LYS16 4.7 16.9 0.0 C C:PRO34 4.7 25.7 1.0 O2A C:GDP201 4.7 16.0 1.0 CB C:ALA59 4.7 24.3 1.0 HB1 C:ALA59 4.7 24.3 0.0 CE2 C:TYR32 4.8 34.2 1.0 CB C:LYS16 4.9 15.2 1.0 NZ C:LYS16 4.9 16.9 1.0 CE C:LYS16 5.0 16.7 1.0

Magnesium binding site 4 out of 4 in the Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A


Mono view


Stereo pair view

A full contact list of Magnesium with other atoms in the Mg binding site number 4 of Crystal Structure of Bit-Blocked Kras-G12V-S39C in Complex with Compound 20A within 5.0Å range: probe atom residue distance (Å) B Occ D:Mg202 b:14.2 occ:1.00 OG D:SER17 1.9 15.2 1.0 O D:HOH321 2.1 15.2 1.0 O D:HOH301 2.1 22.6 1.0 O2B D:GDP201 2.1 18.3 1.0 O D:HOH322 2.3 13.7 1.0 O D:HOH312 2.3 12.6 1.0 H D:SER17 3.1 15.3 0.0 CB D:SER17 3.2 15.5 1.0 HB2 D:SER17 3.3 15.5 0.0 PB D:GDP201 3.4 18.7 1.0 HB2 D:ALA59 3.4 26.7 0.0 O1B D:GDP201 3.6 18.3 1.0 HB2 D:LYS16 3.7 15.5 0.0 HA D:PRO34 3.8 23.6 0.0 N D:SER17 3.8 15.3 1.0 HB3 D:SER17 3.9 15.5 0.0 OD2 D:ASP57 3.9 17.5 1.0 OD1 D:ASP57 3.9 18.9 1.0 HE2 D:LYS16 4.0 15.7 0.0 CA D:SER17 4.1 15.3 1.0 HB1 D:ALA59 4.3 26.7 0.0 O D:HOH332 4.3 42.1 1.0 CG D:ASP57 4.3 17.7 1.0 O1A D:GDP201 4.3 18.6 1.0 CB D:ALA59 4.3 26.7 1.0 O D:THR58 4.4 20.7 1.0 O3A D:GDP201 4.4 17.9 1.0 O D:ILE36 4.4 25.4 1.0 O3B D:GDP201 4.4 18.4 1.0 HA D:SER17 4.4 15.3 0.0 O D:PRO34 4.4 23.2 1.0 HZ3 D:LYS16 4.4 15.7 0.0 O D:ASP33 4.4 25.9 1.0 HZ1 D:LYS16 4.7 15.7 0.0 PA D:GDP201 4.7 18.1 1.0 O2A D:GDP201 4.7 17.1 1.0 CA D:PRO34 4.7 23.6 1.0 HB3 D:TYR32 4.7 28.5 0.0 CB D:LYS16 4.7 15.5 1.0 C D:PRO34 4.8 23.5 1.0 C D:LYS16 4.9 15.4 1.0 NZ D:LYS16 4.9 15.7 1.0 CE D:LYS16 4.9 15.7 1.0 H D:LYS16 4.9 15.3 0.0 HB3 D:ALA59 4.9 26.7 0.0

J.Broker, A.G.Waterson, C.Smethurst, D.Kessler, J.Bottcher, M.Mayer, G.Gmaschitz, J.Phan, A.Little, J.R.Abbott, Q.Sun, M.Gmachl, D.Rudolph, H.Arnhof, K.Rumpel, F.Savarese, T.Gerstberger, N.Mischerikow, M.Treu, L.Herdeis, T.Wunberg, A.Gollner, H.Weinstabl, A.Mantoulidis, O.Kramer, D.B.Mcconnell, S.W Fesik. Fragment Optimization of Reversible Binding to the Switch II Pocket on Kras Leads to A Potent, in Vivo Active Kras G12C Inhibitor. J.Med.Chem. V. 65 14614 2022.
ISSN: ISSN 0022-2623
PubMed: 36300829
DOI: 10.1021/ACS.JMEDCHEM.2C01120