Bromine in PDB 8tsb: Human PI3K P85ALPHA/P110ALPHA Bound to Compound 2

The structure of Human PI3K P85ALPHA/P110ALPHA Bound to Compound 2, PDB code: 8tsb 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)	49.54 / 3.53
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	87.871, 119.947, 189.317, 90, 90, 90
R / Rfree (%)	21.6 / 25.6

The structure of Human PI3K P85ALPHA/P110ALPHA Bound to Compound 2 also contains other interesting chemical elements:

Fluorine

(F)

1 atom

The binding sites of Bromine atom in the Human PI3K P85ALPHA/P110ALPHA Bound to Compound 2 (pdb code 8tsb). This binding sites where shown within 5.0 Angstroms radius around Bromine atom.
In total only one binding site of Bromine was determined in the Human PI3K P85ALPHA/P110ALPHA Bound to Compound 2, PDB code: 8tsb:

Bromine binding site 1 out of 1 in the Human PI3K P85ALPHA/P110ALPHA Bound to Compound 2


Mono view


Stereo pair view

A full contact list of Bromine with other atoms in the Br binding site number 1 of Human PI3K P85ALPHA/P110ALPHA Bound to Compound 2 within 5.0Å range: probe atom residue distance (Å) B Occ A:Br1101 b:138.5 occ:1.00 BR27 A:UIW1101 0.0 138.5 1.0 C26 A:UIW1101 1.9 153.5 1.0 C25 A:UIW1101 2.9 130.8 1.0 C28 A:UIW1101 2.9 156.2 1.0 H251 A:UIW1101 3.0 157.6 1.0 H281 A:UIW1101 3.0 188.1 1.0 HD21 A:LEU812 3.0 197.4 1.0 HG3 A:GLN809 3.0 139.1 1.0 HA A:GLN809 3.2 146.8 1.0 HB3 A:GLN809 3.6 137.6 1.0 HB2 A:GLU1012 3.7 144.8 1.0 CG A:GLN809 3.7 115.3 1.0 HB3 A:LEU812 3.8 131.0 1.0 HG2 A:GLN809 3.9 139.1 1.0 HG2 A:GLU1012 3.9 169.0 1.0 CB A:GLN809 3.9 114.1 1.0 CA A:GLN809 3.9 121.8 1.0 CD2 A:LEU812 4.0 163.9 1.0 HG1 A:THR813 4.1 148.6 1.0 HD11 A:LEU1013 4.1 144.7 1.0 HD12 A:LEU1013 4.1 144.7 1.0 C23 A:UIW1101 4.2 148.8 1.0 C21 A:UIW1101 4.2 152.4 1.0 O A:GLN809 4.2 128.5 1.0 HB3 A:GLU1012 4.2 144.8 1.0 HG A:LEU938 4.3 193.2 1.0 CB A:GLU1012 4.3 120.1 1.0 SD A:MET1010 4.3 120.4 1.0 HD23 A:LEU812 4.3 197.4 1.0 OG1 A:THR813 4.4 123.2 1.0 HG A:LEU812 4.4 135.9 1.0 CG A:GLU1012 4.5 140.3 1.0 HD22 A:LEU812 4.5 197.4 1.0 C A:GLN809 4.5 116.8 1.0 H141 A:UIW1101 4.6 210.0 1.0 CD1 A:LEU1013 4.6 120.0 1.0 CG A:LEU812 4.6 112.7 1.0 CB A:LEU812 4.6 108.7 1.0 H162 A:UIW1101 4.7 208.3 1.0 C22 A:UIW1101 4.7 142.3 1.0 OE1 A:GLU1012 4.7 127.0 1.0 HD21 A:LEU938 4.8 214.5 1.0 HE1 A:PHE1002 4.8 137.1 1.0 CD A:GLU1012 4.8 135.7 1.0 HB2 A:GLN809 4.9 137.6 1.0 HG A:LEU1013 4.9 132.7 1.0 HB3 A:MET1010 5.0 202.8 1.0 HB2 A:LEU812 5.0 131.0 1.0 HE1 A:MET1010 5.0 177.8 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