Fluorine in PDB 8un4: Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One)

Enzymatic activity of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One)

All present enzymatic activity of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One):
3.6.5.2;

Protein crystallography data

The structure of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One), PDB code: 8un4 was solved by M.H.Ultsch, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 42.74 / 1.57
Space group P 21 2 21
Cell size a, b, c (Å), α, β, γ (°) 40.73, 55.69, 85.49, 90, 90, 90
R / Rfree (%) 19 / 21.5

Other elements in 8un4:

The structure of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One) also contains other interesting chemical elements:

Chlorine (Cl) 1 atom
Magnesium (Mg) 1 atom

Fluorine Binding Sites:

The binding sites of Fluorine atom in the Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One) (pdb code 8un4). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One), PDB code: 8un4:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in 8un4

Go back to Fluorine Binding Sites List in 8un4
Fluorine binding site 1 out of 4 in the Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One) within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F203

b:22.6
occ:1.00
 F A:XV3203 0.0 22.6 1.0
C6 A:XV3203 1.3 22.9 1.0
F2 A:XV3203 2.1 21.1 1.0
F1 A:XV3203 2.1 21.7 1.0
C5 A:XV3203 2.4 21.3 1.0
H1 A:XV3203 2.5 26.9 1.0
C1 A:XV3203 3.1 20.3 1.0
C A:XV3203 3.2 22.2 1.0
CB A:GLN99 3.4 26.1 1.0
C4 A:XV3203 3.4 21.1 1.0
O A:TYR96 3.5 21.4 1.0
F3 A:XV3203 3.6 24.8 1.0
H3 A:XV3203 3.6 26.9 1.0
CG1 A:ILE100 3.7 21.3 1.0
CD1 A:TYR96 3.7 19.2 1.0
C7 A:XV3203 3.8 21.4 1.0
CA A:TYR96 3.9 19.0 1.0
C12 A:XV3203 4.0 23.5 1.0
H2 A:XV3203 4.1 26.9 1.0
C A:TYR96 4.2 25.9 1.0
N A:ILE100 4.2 23.4 1.0
CB A:TYR96 4.2 18.5 1.0
CD1 A:ILE100 4.3 20.5 1.0
CG A:GLN99 4.4 22.0 1.0
C2 A:XV3203 4.4 21.3 1.0
CG A:TYR96 4.4 22.8 1.0
C A:GLN99 4.5 25.1 1.0
CA A:GLN99 4.5 23.1 1.0
CG1 A:VAL9 4.5 19.4 1.0
CE1 A:TYR96 4.6 21.0 1.0
N A:XV3203 4.6 22.6 1.0
CB A:VAL9 4.7 15.5 1.0
C8 A:XV3203 4.8 20.4 1.0
CA A:ILE100 4.8 23.9 1.0
CB A:ILE100 4.8 20.8 1.0
CG2 A:VAL9 4.8 17.9 1.0

Fluorine binding site 2 out of 4 in 8un4

Go back to Fluorine Binding Sites List in 8un4
Fluorine binding site 2 out of 4 in the Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One) within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F203

b:21.7
occ:1.00
 F1 A:XV3203 0.0 21.7 1.0
C6 A:XV3203 1.3 22.9 1.0
F2 A:XV3203 2.1 21.1 1.0
F A:XV3203 2.1 22.6 1.0
C5 A:XV3203 2.4 21.3 1.0
C7 A:XV3203 2.7 21.4 1.0
C4 A:XV3203 2.9 21.1 1.0
C8 A:XV3203 3.1 20.4 1.0
C12 A:XV3203 3.3 23.5 1.0
CG1 A:VAL9 3.3 19.4 1.0
CD1 A:TYR96 3.5 19.2 1.0
CL A:XV3203 3.5 21.4 1.0
CB A:VAL9 3.7 15.5 1.0
C1 A:XV3203 3.7 20.3 1.0
F3 A:XV3203 3.7 24.8 1.0
CE1 A:TYR96 3.9 21.0 1.0
C9 A:XV3203 4.0 19.6 1.0
H1 A:XV3203 4.1 26.9 1.0
C11 A:XV3203 4.2 22.8 1.0
N A:XV3203 4.2 22.6 1.0
CE A:MET72 4.3 21.5 1.0
C A:XV3203 4.3 22.2 1.0
H3 A:XV3203 4.4 26.9 1.0
CG2 A:VAL9 4.4 17.9 1.0
O A:HOH382 4.4 20.9 1.0
C10 A:XV3203 4.5 22.8 1.0
H5 A:XV3203 4.6 23.7 1.0
CG A:TYR96 4.7 22.8 1.0
C2 A:XV3203 4.8 21.3 1.0
CA A:VAL9 4.9 18.1 1.0
C3 A:XV3203 5.0 26.6 1.0

Fluorine binding site 3 out of 4 in 8un4

Go back to Fluorine Binding Sites List in 8un4
Fluorine binding site 3 out of 4 in the Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One) within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F203

b:21.1
occ:1.00
 F2 A:XV3203 0.0 21.1 1.0
C6 A:XV3203 1.3 22.9 1.0
F A:XV3203 2.1 22.6 1.0
F1 A:XV3203 2.1 21.7 1.0
C5 A:XV3203 2.4 21.3 1.0
H3 A:XV3203 2.5 26.9 1.0
H1 A:XV3203 2.6 26.9 1.0
C A:XV3203 2.8 22.2 1.0
C1 A:XV3203 2.9 20.3 1.0
CG1 A:VAL9 3.4 19.4 1.0
CE A:MET72 3.5 21.5 1.0
C4 A:XV3203 3.6 21.1 1.0
CG1 A:ILE100 3.6 21.3 1.0
H2 A:XV3203 3.9 26.9 1.0
CE2 A:PHE78 4.1 22.0 1.0
CD1 A:ILE100 4.2 20.5 1.0
C2 A:XV3203 4.2 21.3 1.0
C7 A:XV3203 4.2 21.4 1.0
CD2 A:PHE78 4.2 24.0 1.0
CB A:VAL9 4.3 15.5 1.0
CL A:XV3203 4.6 21.4 1.0
CG2 A:VAL9 4.7 17.9 1.0
N A:XV3203 4.7 22.6 1.0
C8 A:XV3203 4.7 20.4 1.0
CB A:MET72 4.9 20.0 1.0
CG A:MET72 4.9 25.2 1.0
H4 A:XV3203 4.9 25.8 1.0
C3 A:XV3203 4.9 26.6 1.0
CB A:ILE100 4.9 20.8 1.0
C12 A:XV3203 5.0 23.5 1.0
O A:TYR96 5.0 21.4 1.0
SD A:MET72 5.0 26.4 1.0

Fluorine binding site 4 out of 4 in 8un4

Go back to Fluorine Binding Sites List in 8un4
Fluorine binding site 4 out of 4 in the Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Kras-G13D-Gdp in Complex with CPD36 ((E)-1-((3S)-4-(7-(6-Amino-4- Methyl-3-(Trifluoromethyl)Pyridin-2-Yl)-6-Chloro-8-Fluoro-2-(((S)-2- Methylenetetrahydro-1H-Pyrrolizin-7A(5H)-Yl)Methoxy)Quinazolin-4-Yl)- 3-Methylpiperazin-1-Yl)-3-(4-((Dimethylamino)Methyl)-5-Methylpyridin- 2-Yl)Prop-2-En-1-One) within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F203

b:24.8
occ:1.00
 F3 A:XV3203 0.0 24.8 1.0
C12 A:XV3203 1.3 23.5 1.0
C7 A:XV3203 2.3 21.4 1.0
C11 A:XV3203 2.4 22.8 1.0
N1 A:XV3203 2.7 23.8 1.0
C4 A:XV3203 2.8 21.1 1.0
NE2 A:HIS95 3.1 24.1 1.0
OH A:TYR64 3.3 30.9 1.0
C5 A:XV3203 3.3 21.3 1.0
N A:XV3203 3.5 22.6 1.0
O A:HOH316 3.6 43.0 1.0
F A:XV3203 3.6 22.6 1.0
C8 A:XV3203 3.6 20.4 1.0
CG A:GLN99 3.6 22.0 1.0
C10 A:XV3203 3.6 22.8 1.0
F1 A:XV3203 3.7 21.7 1.0
C6 A:XV3203 3.7 22.9 1.0
CE1 A:HIS95 3.8 24.6 1.0
CE1 A:TYR64 3.9 30.2 1.0
CB A:GLN99 4.0 26.1 1.0
CD2 A:HIS95 4.0 23.4 1.0
C13 A:XV3203 4.0 23.6 1.0
CZ A:TYR64 4.1 32.5 1.0
C9 A:XV3203 4.1 19.6 1.0
CE1 A:TYR96 4.3 21.0 1.0
CD1 A:TYR96 4.3 19.2 1.0
C1 A:XV3203 4.3 20.3 1.0
C3 A:XV3203 4.4 26.6 1.0
CD A:GLN99 4.6 29.6 1.0
O1 A:XV3203 4.7 25.1 1.0
C2 A:XV3203 4.8 21.3 1.0
C14 A:XV3203 4.8 22.3 1.0
ND1 A:HIS95 4.8 26.0 1.0
N2 A:XV3203 4.9 22.5 1.0
OE1 A:GLN99 5.0 30.9 1.0
CB A:GLU62 5.0 35.5 1.0
CG A:HIS95 5.0 27.4 1.0
OE2 A:GLU62 5.0 34.2 1.0

Reference:

M.H.Ultsch, C.Nilewski. Structure-Based Design and Evaluation of Reversible Kras G13D Inhibitors To Be Published.
Page generated: Sat Aug 3 01:08:37 2024

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