Fluorine in PDB 4xxs: Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine

All present enzymatic activity of Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine:
3.4.23.46;

The structure of Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine, PDB code: 4xxs was solved by K.D.Parris, J.Pandit, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	27.23 / 1.86
Space group	P 61 2 2
Cell size a, b, c (Å), α, β, γ (°)	102.350, 102.350, 170.550, 90.00, 90.00, 120.00
R / Rfree (%)	18.2 / 20.8

The structure of Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine also contains other interesting chemical elements:

Iodine

(I)

2 atoms

The binding sites of Fluorine atom in the Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine (pdb code 4xxs). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine, PDB code: 4xxs:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine


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 BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:41.1 occ:1.00 F1 A:SI5401 0.0 41.1 1.0 C6 A:SI5401 1.4 39.1 1.0 C5 A:SI5401 2.3 39.1 1.0 C1 A:SI5401 2.4 36.2 1.0 OH A:TYR71 2.9 41.2 1.0 C11 A:SI5401 2.9 35.9 1.0 CZ A:TYR71 3.0 37.9 1.0 C7 A:SI5401 3.1 36.1 1.0 C12 A:SI5401 3.1 36.7 1.0 CD1 A:PHE108 3.3 38.9 1.0 CE1 A:PHE108 3.3 41.4 1.0 CE2 A:TYR71 3.4 39.7 1.0 C4 A:SI5401 3.6 40.8 1.0 C2 A:SI5401 3.6 37.4 1.0 CE1 A:TYR71 3.7 36.8 1.0 O A:HOH531 3.8 49.0 1.0 C13 A:SI5401 3.9 38.4 1.0 C3 A:SI5401 4.1 40.3 1.0 O1 A:SI5401 4.2 38.6 1.0 C9 A:SI5401 4.2 35.2 1.0 CD2 A:TYR71 4.2 37.9 1.0 C8 A:SI5401 4.2 37.9 1.0 N1 A:SI5401 4.4 36.8 1.0 CD1 A:TYR71 4.5 39.7 1.0 CG A:PHE108 4.6 35.7 1.0 CZ A:PHE108 4.7 40.0 1.0 O A:HOH569 4.7 75.6 1.0 F2 A:SI5401 4.7 43.2 1.0 CG A:TYR71 4.8 38.2 1.0 CD1 A:ILE118 4.9 46.8 1.0 O A:HOH518 5.0 39.0 1.0

Fluorine binding site 2 out of 2 in the Crystal Structure of BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine


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 BACE1 with A Pyrazole-Substituted Tetrahydropyran Thioamidine within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:43.2 occ:1.00 F2 A:SI5401 0.0 43.2 1.0 C4 A:SI5401 1.3 40.8 1.0 C3 A:SI5401 2.3 40.3 1.0 C5 A:SI5401 2.3 39.1 1.0 C2 A:DMS406 3.2 94.7 1.0 CZ2 A:TRP115 3.3 37.6 1.0 O A:HOH518 3.4 39.0 1.0 C6 A:SI5401 3.6 39.1 1.0 C2 A:SI5401 3.6 37.4 1.0 CH2 A:TRP115 3.6 37.7 1.0 CD1 A:ILE110 3.8 47.2 1.0 S A:DMS406 4.0 95.2 1.0 CD1 A:LEU30 4.0 45.1 1.0 C1 A:SI5401 4.1 36.2 1.0 O A:PHE108 4.1 39.1 1.0 CG1 A:ILE110 4.4 42.9 1.0 CE2 A:TRP115 4.4 37.8 1.0 O A:HOH569 4.5 75.6 1.0 F1 A:SI5401 4.7 41.1 1.0 CZ3 A:TRP115 4.9 37.1 1.0 CD2 A:LEU30 5.0 48.1 1.0

M.A.Brodney, E.M.Beck, C.R.Butler, G.Barreiro, E.F.Johnson, D.Riddell, K.Parris, C.E.Nolan, Y.Fan, K.Atchison, C.Gonzales, A.Robshaw, S.D.Doran, M.W.Bundesmann, L.M.Buzon, J.K.Dutra, K.E.Henegar, E.A.Lachapelle, X.Hou, B.N.Rogers, J.Pandit, R.Lira, L.A.Martinez-Alsina, P.Mikochik, J.C.Murray, K.Ogilvie, L.Price, S.Sakya, A.Yu, Y.Zhang, B.T.O'neill. Utilizing CYP2D6 and BACE1 Structure Complexes to Reduce Risk of Drug-Drug Interactions with A Novel Series of Centrally Efficacious BACE1 Inhibitors. J.Med.Chem. 2015.
ISSN: ISSN 0022-2623
PubMed: 25781223
DOI: 10.1021/ACS.JMEDCHEM.5B00191