Iodine in PDB 6wny: Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15

All present enzymatic activity of Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15:
3.4.23.46;

The structure of Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15, PDB code: 6wny was solved by D.A.Whittington, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	34.90 / 1.86
Space group	P 61 2 2
Cell size a, b, c (Å), α, β, γ (°)	101.783, 101.783, 171.141, 90.00, 90.00, 120.00
R / Rfree (%)	16.8 / 20.9

The structure of Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15 also contains other interesting chemical elements:

Fluorine

(F)

2 atoms

The binding sites of Iodine atom in the Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15 (pdb code 6wny). This binding sites where shown within 5.0 Angstroms radius around Iodine atom.
In total 3 binding sites of Iodine where determined in the Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15, PDB code: 6wny:
Jump to Iodine binding site number: 1; 2; 3;

Iodine binding site 1 out of 3 in the Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15


Mono view


Stereo pair view

A full contact list of Iodine with other atoms in the I binding site number 1 of Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15 within 5.0Å range: probe atom residue distance (Å) B Occ A:I502 b:52.5 occ:1.00 H A:LYS168 2.7 21.5 1.0 HE2 A:HIS106 3.0 29.2 1.0 HA A:ASP167 3.2 20.7 1.0 O A:HOH989 3.4 29.3 0.5 N A:LYS168 3.5 17.9 1.0 O A:HOH607 3.6 28.1 1.0 O A:HOH806 3.6 16.4 1.0 O A:HOH770 3.6 38.8 1.0 HE2 A:PHE108 3.7 43.0 1.0 NE2 A:HIS106 3.8 24.3 1.0 HA A:LYS168 4.1 20.9 1.0 CA A:ASP167 4.1 17.3 1.0 CE2 A:PHE108 4.2 35.8 1.0 HE1 A:HIS106 4.3 29.4 1.0 OD1 A:ASP167 4.3 34.3 1.0 C A:ASP167 4.3 18.0 1.0 HZ A:PHE108 4.4 45.5 1.0 CA A:LYS168 4.4 17.4 1.0 H A:PHE169 4.4 17.4 1.0 CE1 A:HIS106 4.5 24.5 1.0 O A:SER166 4.5 20.6 1.0 CZ A:PHE108 4.5 37.9 1.0 HG3 A:LYS168 4.6 25.9 1.0 O A:HOH643 4.7 33.7 1.0 N A:ASP167 4.9 15.8 1.0 CG A:ASP167 4.9 29.0 1.0 CD2 A:HIS106 5.0 18.7 1.0 CD2 A:PHE108 5.0 28.2 1.0 C A:SER166 5.0 22.8 1.0

Iodine binding site 2 out of 3 in the Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15


Mono view


Stereo pair view

A full contact list of Iodine with other atoms in the I binding site number 2 of Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15 within 5.0Å range: probe atom residue distance (Å) B Occ A:I503 b:34.6 occ:1.00 HG A:SER166 2.6 23.4 1.0 O A:HOH857 3.1 22.4 1.0 HD2 A:HIS106 3.2 22.4 1.0 HA A:GLU165 3.2 23.2 1.0 HB2 A:HIS106 3.2 20.4 1.0 O A:HOH852 3.3 29.5 1.0 H A:SER166 3.4 20.7 1.0 OG A:SER166 3.4 19.5 1.0 HG22 A:ILE163 3.4 14.4 1.0 HE2 A:PHE170 3.5 18.7 1.0 N A:SER166 3.6 17.2 1.0 CA A:GLU165 3.7 19.3 1.0 C A:GLU165 3.8 17.6 1.0 N A:GLU165 3.8 19.3 1.0 CD2 A:HIS106 3.9 18.7 1.0 HB3 A:SER166 3.9 17.4 1.0 C A:THR164 4.0 25.9 1.0 HB3 A:ALA104 4.1 15.1 1.0 CB A:HIS106 4.1 17.0 1.0 CB A:SER166 4.1 14.5 1.0 H A:GLU165 4.2 23.1 1.0 O A:THR164 4.2 24.7 1.0 CG2 A:ILE163 4.3 12.0 1.0 HG21 A:ILE163 4.3 14.4 1.0 CG A:HIS106 4.4 21.9 1.0 HD2 A:PHE170 4.4 18.0 1.0 CE2 A:PHE170 4.4 15.6 1.0 CA A:SER166 4.5 19.2 1.0 HA A:THR164 4.5 24.7 1.0 O A:ILE163 4.5 12.2 1.0 O A:GLU165 4.6 15.8 1.0 HB3 A:HIS106 4.6 20.4 1.0 CA A:THR164 4.7 20.6 1.0 HG23 A:ILE163 4.7 14.4 1.0 H A:HIS106 4.8 21.8 1.0 CD2 A:PHE170 4.8 15.0 1.0 C A:ILE163 4.9 15.1 1.0 N A:THR164 4.9 15.1 1.0

Iodine binding site 3 out of 3 in the Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15


Mono view


Stereo pair view

A full contact list of Iodine with other atoms in the I binding site number 3 of Crystal Structure of BACE1 in Complex with (Z)-Fluoro-Olefin Containing Compound 15 within 5.0Å range: probe atom residue distance (Å) B Occ A:I504 b:30.5 occ:0.50 O A:HOH825 3.1 16.7 1.0 HE2 A:TYR283 3.3 26.2 1.0 O A:HOH774 3.4 35.2 1.0 HE3 A:LYS300 3.6 41.1 1.0 HG3 A:LYS300 4.0 41.1 1.0 HB3 A:LYS299 4.0 26.0 1.0 CE2 A:TYR283 4.1 21.8 1.0 HD2 A:TYR283 4.1 24.2 1.0 HZ2 A:LYS300 4.1 53.9 1.0 O A:HOH869 4.2 24.1 1.0 HB2 A:LYS300 4.2 33.3 1.0 H A:LYS300 4.3 24.1 1.0 HD2 A:LYS300 4.3 44.1 1.0 CE A:LYS300 4.4 34.3 1.0 CD2 A:TYR283 4.5 20.1 1.0 HD3 A:LYS299 4.6 35.0 1.0 NZ A:LYS300 4.7 44.9 1.0 CG A:LYS300 4.7 34.3 1.0 CD A:LYS300 4.7 36.8 1.0 HH A:TYR283 4.8 29.7 1.0 HZ1 A:LYS300 4.8 53.9 1.0 CB A:LYS300 4.9 27.8 1.0 CB A:LYS299 5.0 21.7 1.0 N A:LYS300 5.0 20.1 1.0

M.Frohn, L.Liu, A.C.Siegmund, W.Qian, A.Amegadzie, N.Chen, H.Tan, D.Hickman, S.Wood, P.H.Wen, M.D.Bartberger, D.A.Whittington, J.R.Allen, M.P.Bourbeau. The Development of A Structurally Distinct Series of BACE1 Inhibitors Via the (Z)-Fluoro-Olefin Amide Bioisosteric Replacement Bioorg.Med.Chem.Lett. 2020.
ISSN: ESSN 1464-3405
DOI: 10.1016/J.BMCL.2020.12724