Fluorine in PDB 8v8u: PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12).

The structure of PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12)., PDB code: 8v8u was solved by R.J.Gunn, J.D.Lawson, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	84.60 / 2.93
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	84.633, 121.859, 163.881, 90, 91.69, 90
R / Rfree (%)	20.3 / 25.5

The binding sites of Fluorine atom in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12). (pdb code 8v8u). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12)., PDB code: 8v8u:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12).


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12). within 5.0Å range: probe atom residue distance (Å) B Occ A:F1100 b:94.0 occ:1.00 F2 A:1LT1100 0.0 94.0 1.0 C18 A:1LT1100 1.4 78.1 1.0 F A:1LT1100 2.2 77.9 1.0 F1 A:1LT1100 2.3 81.4 1.0 C15 A:1LT1100 2.5 68.8 1.0 C17 A:1LT1100 3.0 83.8 1.0 C16 A:1LT1100 3.0 57.6 1.0 NZ A:LYS802 3.4 108.3 1.0 CE A:LYS802 3.4 92.1 1.0 C13 A:1LT1100 3.8 73.3 1.0 CG A:PRO778 3.8 71.6 1.0 OG A:SER774 3.9 112.4 1.0 CD A:LYS802 4.1 87.7 1.0 CB A:PRO778 4.4 66.2 1.0 N4 A:1LT1100 4.4 86.4 1.0 C14 A:1LT1100 4.7 78.4 1.0 CE A:MET772 4.8 88.3 1.0 CB A:SER774 4.8 102.8 1.0 SD A:MET772 4.9 73.5 1.0 CG A:LYS802 5.0 83.5 1.0

Fluorine binding site 2 out of 6 in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12).


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12). within 5.0Å range: probe atom residue distance (Å) B Occ A:F1100 b:77.9 occ:1.00 F A:1LT1100 0.0 77.9 1.0 C18 A:1LT1100 1.3 78.1 1.0 F2 A:1LT1100 2.2 94.0 1.0 F1 A:1LT1100 2.2 81.4 1.0 C15 A:1LT1100 2.4 68.8 1.0 C13 A:1LT1100 2.9 73.3 1.0 N4 A:1LT1100 2.9 86.4 1.0 C17 A:1LT1100 2.9 83.8 1.0 NZ A:LYS802 3.1 108.3 1.0 CE A:LYS802 3.5 92.1 1.0 CD A:LYS802 3.6 87.7 1.0 CD1 A:ILE848 3.6 74.2 1.0 C16 A:1LT1100 3.7 57.6 1.0 C12 A:1LT1100 4.0 88.1 1.0 C14 A:1LT1100 4.0 78.4 1.0 CG A:LYS802 4.7 83.5 1.0 C10 A:1LT1100 4.9 76.0 1.0 C11 A:1LT1100 4.9 71.1 1.0

Fluorine binding site 3 out of 6 in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12).


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12). within 5.0Å range: probe atom residue distance (Å) B Occ A:F1100 b:81.4 occ:1.00 F1 A:1LT1100 0.0 81.4 1.0 C18 A:1LT1100 1.4 78.1 1.0 F A:1LT1100 2.2 77.9 1.0 F2 A:1LT1100 2.3 94.0 1.0 C15 A:1LT1100 2.4 68.8 1.0 C13 A:1LT1100 2.9 73.3 1.0 C16 A:1LT1100 2.9 57.6 1.0 C14 A:1LT1100 3.3 78.4 1.0 CG2 A:ILE800 3.5 60.1 1.0 CD1 A:ILE800 3.6 66.4 1.0 N4 A:1LT1100 3.6 86.4 1.0 C17 A:1LT1100 3.8 83.8 1.0 SD A:MET772 4.2 73.5 1.0 CD1 A:ILE848 4.2 74.2 1.0 CB A:ILE800 4.3 57.8 1.0 CE A:MET772 4.3 88.3 1.0 C10 A:1LT1100 4.4 76.0 1.0 CG1 A:ILE800 4.5 64.5 1.0 C12 A:1LT1100 4.6 88.1 1.0 CB A:PRO778 4.7 66.2 1.0 CG A:PRO778 4.9 71.6 1.0 CE A:LYS802 4.9 92.1 1.0 CD A:LYS802 4.9 87.7 1.0 NZ A:LYS802 4.9 108.3 1.0 C11 A:1LT1100 4.9 71.1 1.0

Fluorine binding site 4 out of 6 in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12).


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12). within 5.0Å range: probe atom residue distance (Å) B Occ C:F1100 b:100.4 occ:1.00 F2 C:1LT1100 0.0 100.4 1.0 C18 C:1LT1100 1.4 80.0 1.0 F C:1LT1100 2.2 83.9 1.0 F1 C:1LT1100 2.3 73.8 1.0 C15 C:1LT1100 2.5 67.8 1.0 C16 C:1LT1100 3.0 61.4 1.0 C17 C:1LT1100 3.0 81.7 1.0 NZ C:LYS802 3.4 107.5 1.0 CE C:LYS802 3.5 83.3 1.0 C13 C:1LT1100 3.8 82.9 1.0 CG C:PRO778 4.0 70.8 1.0 CD C:LYS802 4.3 75.8 1.0 N4 C:1LT1100 4.4 87.5 1.0 OG C:SER774 4.5 104.1 1.0 CB C:PRO778 4.5 63.7 1.0 C14 C:1LT1100 4.7 87.2 1.0 CE C:MET772 4.8 85.3 1.0 CG2 C:ILE800 5.0 64.7 1.0

Fluorine binding site 5 out of 6 in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12).


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12). within 5.0Å range: probe atom residue distance (Å) B Occ C:F1100 b:83.9 occ:1.00 F C:1LT1100 0.0 83.9 1.0 C18 C:1LT1100 1.3 80.0 1.0 F2 C:1LT1100 2.2 100.4 1.0 F1 C:1LT1100 2.2 73.8 1.0 C15 C:1LT1100 2.4 67.8 1.0 C13 C:1LT1100 2.9 82.9 1.0 C17 C:1LT1100 2.9 81.7 1.0 N4 C:1LT1100 2.9 87.5 1.0 NZ C:LYS802 3.2 107.5 1.0 CD1 C:ILE848 3.3 90.1 1.0 CE C:LYS802 3.6 83.3 1.0 C16 C:1LT1100 3.7 61.4 1.0 CD C:LYS802 3.8 75.8 1.0 C14 C:1LT1100 4.0 87.2 1.0 C12 C:1LT1100 4.0 90.7 1.0 CG2 C:ILE800 4.7 64.7 1.0 CG1 C:ILE848 4.7 77.1 1.0 C10 C:1LT1100 4.8 73.9 1.0 CG C:LYS802 4.8 75.2 1.0 C11 C:1LT1100 4.9 83.4 1.0

Fluorine binding site 6 out of 6 in the PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12).


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of PI3KA H1047R Co-Crystal Structure with Inhibitor in Cryptic Pocket Near H1047R (Compound 12). within 5.0Å range: probe atom residue distance (Å) B Occ C:F1100 b:73.8 occ:1.00 F1 C:1LT1100 0.0 73.8 1.0 C18 C:1LT1100 1.4 80.0 1.0 F C:1LT1100 2.2 83.9 1.0 F2 C:1LT1100 2.3 100.4 1.0 C15 C:1LT1100 2.4 67.8 1.0 C16 C:1LT1100 2.9 61.4 1.0 C13 C:1LT1100 2.9 82.9 1.0 C14 C:1LT1100 3.2 87.2 1.0 CG2 C:ILE800 3.4 64.7 1.0 CD1 C:ILE800 3.6 72.4 1.0 N4 C:1LT1100 3.7 87.5 1.0 C17 C:1LT1100 3.8 81.7 1.0 CE C:MET772 3.8 85.3 1.0 CB C:ILE800 4.3 58.5 1.0 SD C:MET772 4.3 75.7 1.0 C10 C:1LT1100 4.3 73.9 1.0 CD1 C:ILE848 4.4 90.1 1.0 CG1 C:ILE800 4.5 57.6 1.0 C12 C:1LT1100 4.7 90.7 1.0 CB C:PRO778 4.8 63.7 1.0 C11 C:1LT1100 4.9 83.4 1.0 CG C:PRO778 4.9 70.8 1.0

J.M.Ketcham, S.J.Harwood, R.Aranda, A.N.Aloiau, B.M.Bobek, D.M.Briere, A.C.Burns, K.C.Haatveit, A.Calinisan, J.Clarine, A.Elliott, L.D.Engstrom, R.J.Gunn, A.Ivetac, B.Jones, J.Kuehler, J.D.Lawson, N.Nguyen, C.Parker, K.E.Pearson, L.Rahbaek, B.Saechao, X.Wang, A.Waters, L.Waters, A.H.Watkins, P.Olson, C.R.Smith, J.G.Christensen, M.A.Marx. Discovery of Pyridopyrimidinones That Selectively Inhibit the H1047R PI3K Alpha Mutant Protein J.Med.Chem. 2024.
ISSN: ISSN 0022-2623
DOI: 10.1021/ACS.JMEDCHEM.4C00078