Fluorine in PDB 8tsd: Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608

The structure of Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608, PDB code: 8tsd was solved by M.Holliday, Y.Tang, A.Bulku, J.Wilbur, J.Fraser, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	102.78 / 2.70
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	86.902, 121.522, 192.652, 90, 90, 90
R / Rfree (%)	23.9 / 27.7

The structure of Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608 also contains other interesting chemical elements:

Chlorine

(Cl)

1 atom

The binding sites of Fluorine atom in the Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608 (pdb code 8tsd). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 5 binding sites of Fluorine where determined in the Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608, PDB code: 8tsd:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5;

Fluorine binding site 1 out of 5 in the Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:93.7 occ:1.00 F01 A:XUZ1101 0.0 93.7 1.0 C02 A:XUZ1101 1.3 90.1 1.0 C03 A:XUZ1101 2.4 92.1 1.0 HA A:LEU911 2.4 102.9 1.0 C08 A:XUZ1101 2.4 92.2 1.0 H031 A:XUZ1101 2.5 111.0 1.0 H081 A:XUZ1101 2.6 111.1 1.0 HD1 A:TYR1021 2.6 114.2 1.0 HB A:ILE1022 2.8 117.5 1.0 O A:ILE910 2.9 92.5 1.0 HG13 A:ILE1022 3.0 108.2 1.0 HA A:ILE1022 3.2 114.1 1.0 CA A:LEU911 3.2 85.3 1.0 CB A:ILE1022 3.4 97.5 1.0 HD21 A:LEU911 3.5 113.1 1.0 CD1 A:TYR1021 3.5 94.8 1.0 C A:LEU911 3.5 93.9 1.0 CG1 A:ILE1022 3.6 89.7 1.0 C04 A:XUZ1101 3.6 97.3 1.0 CA A:ILE1022 3.6 94.7 1.0 HD12 A:ILE1022 3.6 119.1 1.0 O A:LEU911 3.7 83.2 1.0 C07 A:XUZ1101 3.7 101.8 1.0 N A:ILE1022 3.8 100.3 1.0 H A:ILE1022 3.8 120.9 1.0 C A:ILE910 3.8 93.5 1.0 HE1 A:TYR1021 3.9 112.2 1.0 HB3 A:TYR1021 4.0 116.2 1.0 N A:LEU911 4.0 87.4 1.0 HG1 A:THR1025 4.1 118.4 1.0 C05 A:XUZ1101 4.1 101.8 1.0 HD22 A:LEU911 4.1 113.1 1.0 CE1 A:TYR1021 4.1 93.1 1.0 CD1 A:ILE1022 4.1 98.8 1.0 CD2 A:LEU911 4.2 93.8 1.0 H181 A:XUZ1101 4.2 114.6 1.0 HB3 A:LEU911 4.2 110.7 1.0 N A:GLY912 4.3 89.4 1.0 CB A:LEU911 4.3 91.9 1.0 H041 A:XUZ1101 4.4 117.3 1.0 C A:TYR1021 4.4 95.5 1.0 H221 A:XUZ1101 4.4 103.7 1.0 HG22 A:ILE910 4.4 105.6 1.0 HG12 A:ILE1022 4.5 108.2 1.0 CG A:TYR1021 4.5 92.1 1.0 HD11 A:ILE1022 4.5 119.1 1.0 H A:GLY912 4.6 107.8 1.0 OG1 A:THR1025 4.7 98.2 1.0 CB A:TYR1021 4.7 96.4 1.0 HG23 A:ILE910 4.7 105.6 1.0 O A:TYR1021 4.8 94.6 1.0 HA3 A:GLY912 4.8 111.8 1.0 H A:LEU911 4.8 105.4 1.0 CG A:LEU911 4.8 82.2 1.0 CG2 A:ILE1022 4.8 101.7 1.0 N18 A:XUZ1101 4.9 95.1 1.0 HD13 A:ILE1022 4.9 119.1 1.0 HD23 A:LEU911 5.0 113.1 1.0 C09 A:XUZ1101 5.0 100.4 1.0 HG21 A:ILE1022 5.0 122.5 1.0

Fluorine binding site 2 out of 5 in the Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:95.1 occ:1.00 F24 A:XUZ1101 0.0 95.1 1.0 C23 A:XUZ1101 1.3 95.9 1.0 C25 A:XUZ1101 2.4 98.2 1.0 C22 A:XUZ1101 2.4 86.0 1.0 HD12 A:LEU911 2.5 97.6 1.0 H221 A:XUZ1101 2.5 103.7 1.0 HB3 A:LEU911 2.5 110.7 1.0 H251 A:XUZ1101 2.6 118.3 1.0 HD22 A:LEU911 2.9 113.1 1.0 HG22 A:THR813 3.1 103.2 1.0 HZ A:PHE1002 3.2 95.8 1.0 CD1 A:LEU911 3.4 80.9 1.0 CB A:LEU911 3.4 91.9 1.0 HD11 A:ILE913 3.5 145.5 1.0 C26 A:XUZ1101 3.6 88.0 1.0 CG A:LEU911 3.6 82.2 1.0 CD2 A:LEU911 3.6 93.8 1.0 C21 A:XUZ1101 3.7 96.6 1.0 HA A:THR813 3.7 92.6 1.0 HB2 A:LEU911 3.8 110.7 1.0 OG1 A:THR813 3.9 86.8 1.0 HD11 A:LEU911 3.9 97.6 1.0 CG2 A:THR813 3.9 85.6 1.0 HD13 A:LEU911 4.0 97.6 1.0 CZ A:PHE1002 4.1 79.4 1.0 C27 A:XUZ1101 4.1 97.4 1.0 HG21 A:THR813 4.1 103.2 1.0 HD23 A:LEU911 4.2 113.1 1.0 HE1 A:PHE1002 4.2 92.7 1.0 CB A:THR813 4.3 79.8 1.0 HG12 A:ILE913 4.3 110.2 1.0 O A:LEU911 4.3 83.2 1.0 HD21 A:LEU911 4.3 113.1 1.0 CD1 A:ILE913 4.4 120.8 1.0 CA A:THR813 4.4 76.8 1.0 HG1 A:THR813 4.4 104.6 1.0 CA A:LEU911 4.5 85.3 1.0 HA A:LEU911 4.5 102.9 1.0 CE1 A:PHE1002 4.6 76.9 1.0 HG13 A:ILE816 4.6 96.4 1.0 HG A:LEU911 4.6 99.2 1.0 HD12 A:ILE913 4.6 145.5 1.0 HG23 A:THR813 4.6 103.2 1.0 HG13 A:ILE913 4.6 110.2 1.0 HG23 A:ILE816 4.7 96.3 1.0 HB A:ILE816 4.7 96.8 1.0 CG1 A:ILE913 4.7 91.4 1.0 H181 A:XUZ1101 4.7 114.6 1.0 C A:LEU911 4.9 93.9 1.0 C28 A:XUZ1101 4.9 90.5 1.0 C19 A:XUZ1101 5.0 98.1 1.0

Fluorine binding site 3 out of 5 in the Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:92.6 occ:1.00 F29 A:XUZ1101 0.0 92.6 1.0 C28 A:XUZ1101 1.3 90.5 1.0 F30 A:XUZ1101 2.1 104.1 1.0 F31 A:XUZ1101 2.1 93.5 1.0 C26 A:XUZ1101 2.4 88.0 1.0 HD21 A:LEU812 2.4 111.3 1.0 HD23 A:LEU812 2.5 111.3 1.0 CD2 A:LEU812 2.8 92.4 1.0 HB3 A:LEU812 3.0 90.1 1.0 H251 A:XUZ1101 3.1 118.3 1.0 C25 A:XUZ1101 3.2 98.2 1.0 HD11 A:LEU1013 3.2 112.7 1.0 HD12 A:LEU1013 3.3 112.7 1.0 C27 A:XUZ1101 3.4 97.4 1.0 H271 A:XUZ1101 3.5 117.3 1.0 HE1 A:PHE1002 3.5 92.7 1.0 HA A:GLN809 3.5 96.5 1.0 HG A:LEU812 3.6 98.5 1.0 CG A:LEU812 3.6 81.7 1.0 HD22 A:LEU812 3.7 111.3 1.0 CB A:LEU812 3.7 74.7 1.0 CD1 A:LEU1013 3.7 93.5 1.0 HG3 A:GLN809 3.9 98.3 1.0 SD A:MET1010 4.0 100.3 1.0 HB2 A:LEU812 4.1 90.1 1.0 HB2 A:GLU1012 4.2 99.9 1.0 HE1 A:MET1010 4.3 102.0 1.0 HG1 A:THR813 4.3 104.6 1.0 HD13 A:LEU1013 4.4 112.7 1.0 CE1 A:PHE1002 4.4 76.9 1.0 O A:GLN809 4.4 77.1 1.0 CA A:GLN809 4.4 80.0 1.0 C23 A:XUZ1101 4.4 95.9 1.0 HG A:LEU1013 4.5 95.5 1.0 HB3 A:GLN809 4.6 98.3 1.0 HD1 A:PHE1002 4.6 91.5 1.0 C21 A:XUZ1101 4.6 96.6 1.0 CE A:MET1010 4.7 84.6 1.0 CG A:GLN809 4.7 81.5 1.0 CG A:LEU1013 4.7 79.2 1.0 OG1 A:THR813 4.8 86.8 1.0 CB A:GLN809 4.8 81.6 1.0 H A:THR813 4.8 92.0 1.0 HE2 A:MET1010 4.8 102.0 1.0 HB3 A:GLU1012 4.9 99.9 1.0 C A:GLN809 4.9 84.4 1.0 O A:ARG808 4.9 78.8 1.0 CB A:GLU1012 4.9 82.8 1.0 CD1 A:PHE1002 5.0 75.9 1.0

Fluorine binding site 4 out of 5 in the Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:104.1 occ:1.00 F30 A:XUZ1101 0.0 104.1 1.0 C28 A:XUZ1101 1.3 90.5 1.0 F31 A:XUZ1101 2.1 93.5 1.0 F29 A:XUZ1101 2.1 92.6 1.0 HA A:GLN809 2.3 96.5 1.0 C26 A:XUZ1101 2.4 88.0 1.0 O A:GLN809 2.6 77.1 1.0 HG1 A:THR813 2.6 104.6 1.0 H251 A:XUZ1101 2.7 118.3 1.0 HB3 A:GLN809 2.8 98.3 1.0 CA A:GLN809 2.9 80.0 1.0 C25 A:XUZ1101 2.9 98.2 1.0 HB3 A:LEU812 3.1 90.1 1.0 C A:GLN809 3.1 84.4 1.0 OG1 A:THR813 3.2 86.8 1.0 CB A:GLN809 3.2 81.6 1.0 HG3 A:GLN809 3.2 98.3 1.0 C27 A:XUZ1101 3.6 97.4 1.0 CG A:GLN809 3.7 81.5 1.0 H A:THR813 3.7 92.0 1.0 H271 A:XUZ1101 3.8 117.3 1.0 HD21 A:LEU812 3.9 111.3 1.0 HG2 A:GLN809 4.0 98.3 1.0 CB A:LEU812 4.0 74.7 1.0 HB2 A:GLN809 4.1 98.3 1.0 N A:THR813 4.2 76.3 1.0 HD23 A:LEU812 4.2 111.3 1.0 N A:GLN809 4.3 77.4 1.0 C23 A:XUZ1101 4.3 95.9 1.0 HG A:LEU812 4.4 98.5 1.0 O A:ARG808 4.4 78.8 1.0 CD2 A:LEU812 4.4 92.4 1.0 N A:ASP810 4.4 79.2 1.0 CB A:THR813 4.5 79.8 1.0 HB2 A:LEU812 4.5 90.1 1.0 H A:LEU812 4.5 89.0 1.0 CG A:LEU812 4.5 81.7 1.0 HD22 A:LEU938 4.7 144.8 1.0 SD A:MET1010 4.7 100.3 1.0 C21 A:XUZ1101 4.8 96.6 1.0 HG A:LEU938 4.8 145.2 1.0 C A:ARG808 4.8 79.8 1.0 CA A:THR813 4.8 76.8 1.0 C A:LEU812 4.8 77.3 1.0 HB A:THR813 4.8 96.2 1.0 H A:GLN809 4.8 93.3 1.0 CA A:LEU812 4.8 76.6 1.0 HA A:THR813 4.9 92.6 1.0 HD21 A:LEU938 4.9 144.8 1.0 HG2 A:GLU1012 4.9 94.9 1.0 HE1 A:PHE1002 5.0 92.7 1.0 N A:LEU812 5.0 73.8 1.0 H A:ASP810 5.0 95.5 1.0

Fluorine binding site 5 out of 5 in the Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Human PI3K P85ALPHA/P110ALPHA Bound to Rly-2608 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:93.5 occ:1.00 F31 A:XUZ1101 0.0 93.5 1.0 C28 A:XUZ1101 1.3 90.5 1.0 F30 A:XUZ1101 2.1 104.1 1.0 F29 A:XUZ1101 2.1 92.6 1.0 C26 A:XUZ1101 2.4 88.0 1.0 H271 A:XUZ1101 2.4 117.3 1.0 HG3 A:GLN809 2.6 98.3 1.0 C27 A:XUZ1101 2.8 97.4 1.0 HB2 A:GLU1012 3.0 99.9 1.0 HG2 A:GLU1012 3.1 94.9 1.0 CG A:GLN809 3.3 81.5 1.0 HG2 A:GLN809 3.3 98.3 1.0 HA A:GLN809 3.3 96.5 1.0 HB3 A:GLN809 3.4 98.3 1.0 CG A:GLU1012 3.6 78.7 1.0 CB A:GLU1012 3.6 82.8 1.0 HB3 A:GLU1012 3.6 99.9 1.0 C25 A:XUZ1101 3.7 98.2 1.0 CB A:GLN809 3.7 81.6 1.0 CD A:GLU1012 3.7 91.1 1.0 OE1 A:GLU1012 3.9 89.4 1.0 HG A:LEU938 3.9 145.2 1.0 H251 A:XUZ1101 4.0 118.3 1.0 CA A:GLN809 4.0 80.0 1.0 C21 A:XUZ1101 4.2 96.6 1.0 HD12 A:LEU1013 4.3 112.7 1.0 OE2 A:GLU1012 4.3 90.8 1.0 SD A:MET1010 4.4 100.3 1.0 HD21 A:LEU812 4.4 111.3 1.0 HE21 A:GLN809 4.4 97.7 1.0 HG3 A:GLU1012 4.5 94.9 1.0 HB3 A:MET1010 4.5 124.9 1.0 HD11 A:LEU1013 4.6 112.7 1.0 HD23 A:LEU812 4.6 111.3 1.0 CD A:GLN809 4.6 86.4 1.0 O A:GLN809 4.6 77.1 1.0 HB2 A:GLN809 4.6 98.3 1.0 HB3 A:LEU812 4.6 90.1 1.0 HG1 A:THR813 4.7 104.6 1.0 C A:GLN809 4.8 84.4 1.0 HD22 A:LEU938 4.8 144.8 1.0 C23 A:XUZ1101 4.8 95.9 1.0 CG A:LEU938 4.8 120.6 1.0 HG A:LEU1013 4.8 95.5 1.0 CD1 A:LEU1013 4.9 93.5 1.0 NE2 A:GLN809 4.9 81.0 1.0 H A:GLU1012 4.9 108.7 1.0 CD2 A:LEU812 4.9 92.4 1.0 O20 A:XUZ1101 5.0 101.4 1.0 HD21 A:LEU938 5.0 144.8 1.0

A.Varkaris, E.Pazolli, H.Gunaydin, Q.Wang, L.Pierce, A.A.Boezio, L.Dipietro, A.Frost, F.Giordanetto, E.P.Hamilton, K.Harris, M.Holliday, T.L.Hunter, A.Iskandar, Y.Ji, A.Larivee, J.R.Larochelle, A.Lescarbeau, F.Llambi, B.Lormil, M.M.Mader, B.G.Mar, I.Martin, T.H.Mclean, K.Michelsen, Y.Pechersky, E.Puente-Poushnejad, R.Samadani, A.M.Schram, K.Shortsleeves, S.Swaminathan, S.Tajmir, G.Tan, Y.Tang, R.Valverde, B.Wehrenberg, J.Wilbur, B.R.Williams, H.Zeng, W.P.Walters, B.B.Wolf, D.E.Shaw, D.A.Bergstrom, J.Watters, J.S.Fraser, P.D.Fortin, D.R.Kipp. Discovery and Clinical Proof-of-Concept of Rly-2608, A First-in-Class Mutant-Selective Allosteric PI3KA Inhibitor That Decouples Anti-Tumor Activity From Hyperinsulinemia. Cancer Discov 2023.
ISSN: ESSN 2159-8290
PubMed: 37916956
DOI: 10.1158/2159-8290.CD-23-0944