Fluorine in PDB 8exu: Crystal Structure of PI3K-Alpha in Complex with Compound 30

All present enzymatic activity of Crystal Structure of PI3K-Alpha in Complex with Compound 30:
2.7.1.137; 2.7.1.153; 2.7.11.1;

The structure of Crystal Structure of PI3K-Alpha in Complex with Compound 30, PDB code: 8exu was solved by J.R.Kiefer, C.Eigenbrot, S.T.Staben, E.J.Hanan, H.J.A.Wallweber, M.Ultsch, M.G.Braun, L.S.Friedman, H.E.Purkey, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	29.46 / 2.68
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	58.641, 133.719, 140.952, 90, 90, 90
R / Rfree (%)	19.6 / 24.1

The binding sites of Fluorine atom in the Crystal Structure of PI3K-Alpha in Complex with Compound 30 (pdb code 8exu). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Crystal Structure of PI3K-Alpha in Complex with Compound 30, PDB code: 8exu:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Crystal Structure of PI3K-Alpha in Complex with Compound 30


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of PI3K-Alpha in Complex with Compound 30 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:56.3 occ:1.00 F32 A:X3R1101 0.0 56.3 1.0 C31 A:X3R1101 1.4 53.5 1.0 F33 A:X3R1101 2.3 56.3 1.0 F34 A:X3R1101 2.3 52.6 1.0 C25 A:X3R1101 2.4 49.9 1.0 C27 A:X3R1101 2.8 49.1 1.0 N24 A:X3R1101 3.1 50.5 1.0 O28 A:X3R1101 3.2 49.6 1.0 H26 A:X3R1101 3.4 49.5 1.0 C29 A:X3R1101 3.4 52.1 1.0 CD1 A:ILE848 3.5 52.3 1.0 CD A:LYS802 3.6 47.6 1.0 CE A:LYS802 3.7 54.6 1.0 NZ A:LYS802 3.9 62.4 1.0 C22 A:X3R1101 4.0 47.5 1.0 CG2 A:ILE800 4.2 45.7 1.0 CG A:PRO778 4.2 59.8 1.0 CG A:LYS802 4.4 44.2 1.0 O30 A:X3R1101 4.4 53.3 1.0 O A:HOH1250 4.6 68.0 1.0 N21 A:X3R1101 4.6 45.6 1.0 CB A:PRO778 4.6 53.9 1.0 CB A:LYS802 4.8 41.6 1.0 CG1 A:ILE848 5.0 45.6 1.0

Fluorine binding site 2 out of 3 in the Crystal Structure of PI3K-Alpha in Complex with Compound 30


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of PI3K-Alpha in Complex with Compound 30 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:56.3 occ:1.00 F33 A:X3R1101 0.0 56.3 1.0 C31 A:X3R1101 1.4 53.5 1.0 F34 A:X3R1101 2.2 52.6 1.0 F32 A:X3R1101 2.3 56.3 1.0 C25 A:X3R1101 2.4 49.9 1.0 N24 A:X3R1101 2.8 50.5 1.0 H26 A:X3R1101 2.8 49.5 1.0 N21 A:X3R1101 2.9 45.6 1.0 C22 A:X3R1101 2.9 47.5 1.0 CD1 A:ILE800 3.2 38.4 1.0 CG2 A:ILE800 3.4 45.7 1.0 CE A:MET772 3.7 67.2 1.0 C27 A:X3R1101 3.8 49.1 1.0 C20 A:X3R1101 3.8 43.9 1.0 C29 A:X3R1101 3.9 52.1 1.0 C23 A:X3R1101 4.0 45.6 1.0 CG1 A:ILE800 4.0 43.7 1.0 CB A:ILE800 4.1 43.9 1.0 SD A:MET772 4.2 69.2 1.0 CD1 A:ILE848 4.2 52.3 1.0 O28 A:X3R1101 4.3 49.6 1.0 N19 A:X3R1101 4.5 41.8 1.0 CG2 A:ILE848 4.6 47.4 1.0 CG A:PRO778 4.6 59.8 1.0 C2 A:X3R1101 4.6 45.6 1.0 C3 A:X3R1101 4.7 42.9 1.0 O30 A:X3R1101 4.8 53.3 1.0 CB A:ILE848 4.9 45.7 1.0

Fluorine binding site 3 out of 3 in the Crystal Structure of PI3K-Alpha in Complex with Compound 30


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of PI3K-Alpha in Complex with Compound 30 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:52.6 occ:1.00 F34 A:X3R1101 0.0 52.6 1.0 C31 A:X3R1101 1.4 53.5 1.0 F33 A:X3R1101 2.2 56.3 1.0 F32 A:X3R1101 2.3 56.3 1.0 C25 A:X3R1101 2.4 49.9 1.0 H26 A:X3R1101 2.5 49.5 1.0 OG A:SER774 3.1 86.1 1.0 C27 A:X3R1101 3.1 49.1 1.0 CB A:SER774 3.3 74.8 1.0 CE A:MET772 3.5 67.2 1.0 CG A:PRO778 3.5 59.8 1.0 N24 A:X3R1101 3.7 50.5 1.0 O A:HOH1285 4.2 46.5 1.0 O28 A:X3R1101 4.3 49.6 1.0 SD A:MET772 4.3 69.2 1.0 N21 A:X3R1101 4.3 45.6 1.0 C22 A:X3R1101 4.4 47.5 1.0 C29 A:X3R1101 4.5 52.1 1.0 CD A:PRO778 4.5 57.0 1.0 CB A:PRO778 4.6 53.9 1.0 CG2 A:ILE800 4.7 45.7 1.0 CA A:SER774 4.8 72.9 1.0

E.J.Hanan, M.G.Braun, R.A.Heald, C.Macleod, C.Chan, S.Clausen, K.A.Edgar, C.Eigenbrot, R.Elliott, N.Endres, L.S.Friedman, E.Gogol, X.H.Gu, R.H.Thibodeau, P.S.Jackson, J.R.Kiefer, J.D.Knight, M.Nannini, R.Narukulla, A.Pace, J.Pang, H.E.Purkey, L.Salphati, D.Sampath, S.Schmidt, S.Sideris, K.Song, S.Sujatha-Bhaskar, M.Ultsch, H.Wallweber, J.Xin, S.Yeap, A.Young, Y.Zhong, S.T.Staben. Discovery of Gdc-0077 (Inavolisib), A Highly Selective Inhibitor and Degrader of Mutant PI3K Alpha. J.Med.Chem. V. 65 16589 2022.
ISSN: ISSN 0022-2623
PubMed: 36455032
DOI: 10.1021/ACS.JMEDCHEM.2C01422