Fluorine in PDB 7n66: Bace-1 in Complex with Ligand 12
Enzymatic activity of Bace-1 in Complex with Ligand 12
All present enzymatic activity of Bace-1 in Complex with Ligand 12:
3.4.23.46;
Protein crystallography data
The structure of Bace-1 in Complex with Ligand 12, PDB code: 7n66
was solved by
P.L.Shaffer,
with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:
Resolution Low / High (Å)
|
19.91 /
2.10
|
Space group
|
P 61 2 2
|
Cell size a, b, c (Å), α, β, γ (°)
|
102.13,
102.13,
170.523,
90,
90,
120
|
R / Rfree (%)
|
19.6 /
23
|
Other elements in 7n66:
The structure of Bace-1 in Complex with Ligand 12 also contains other interesting chemical elements:
Fluorine Binding Sites:
The binding sites of Fluorine atom in the Bace-1 in Complex with Ligand 12
(pdb code 7n66). This binding sites where shown within
5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the
Bace-1 in Complex with Ligand 12, PDB code: 7n66:
Jump to Fluorine binding site number:
1;
2;
3;
4;
Fluorine binding site 1 out
of 4 in 7n66
Go back to
Fluorine Binding Sites List in 7n66
Fluorine binding site 1 out
of 4 in the Bace-1 in Complex with Ligand 12
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 1 of Bace-1 in Complex with Ligand 12 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F510
b:26.4
occ:1.00
|
F3
|
A:0EW510
|
0.0
|
26.4
|
1.0
|
C19
|
A:0EW510
|
1.3
|
26.4
|
1.0
|
F2
|
A:0EW510
|
2.2
|
26.5
|
1.0
|
O4
|
A:0EW510
|
2.2
|
25.7
|
1.0
|
O3
|
A:0EW510
|
2.2
|
26.6
|
1.0
|
C20
|
A:0EW510
|
3.1
|
25.9
|
1.0
|
C18
|
A:0EW510
|
3.1
|
26.1
|
1.0
|
N
|
A:GLY13
|
3.5
|
26.6
|
1.0
|
CE1
|
A:TYR14
|
3.5
|
23.5
|
1.0
|
CA
|
A:GLY13
|
3.6
|
24.7
|
1.0
|
CD1
|
A:TYR14
|
3.9
|
23.3
|
1.0
|
N
|
A:GLY11
|
4.1
|
35.7
|
1.0
|
NH2
|
A:ARG307
|
4.3
|
28.5
|
1.0
|
N
|
A:GLN12
|
4.3
|
26.4
|
1.0
|
C
|
A:GLY13
|
4.3
|
25.1
|
1.0
|
C21
|
A:0EW510
|
4.3
|
25.3
|
1.0
|
CA
|
A:GLY11
|
4.4
|
31.9
|
1.0
|
OE2
|
A:GLU339
|
4.4
|
29.0
|
1.0
|
C17
|
A:0EW510
|
4.4
|
25.7
|
1.0
|
CZ
|
A:TYR14
|
4.4
|
26.6
|
1.0
|
C
|
A:GLY11
|
4.5
|
27.7
|
1.0
|
O
|
A:LYS9
|
4.5
|
43.9
|
1.0
|
CB
|
A:ALA335
|
4.5
|
20.3
|
1.0
|
C
|
A:GLN12
|
4.7
|
31.1
|
1.0
|
OH
|
A:TYR14
|
4.7
|
30.6
|
1.0
|
O
|
A:GLY13
|
4.7
|
25.2
|
1.0
|
OG1
|
A:THR232
|
4.9
|
19.6
|
1.0
|
N
|
A:TYR14
|
5.0
|
19.4
|
1.0
|
|
Fluorine binding site 2 out
of 4 in 7n66
Go back to
Fluorine Binding Sites List in 7n66
Fluorine binding site 2 out
of 4 in the Bace-1 in Complex with Ligand 12
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 2 of Bace-1 in Complex with Ligand 12 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F510
b:26.5
occ:1.00
|
F2
|
A:0EW510
|
0.0
|
26.5
|
1.0
|
C19
|
A:0EW510
|
1.3
|
26.4
|
1.0
|
F3
|
A:0EW510
|
2.2
|
26.4
|
1.0
|
O4
|
A:0EW510
|
2.3
|
25.7
|
1.0
|
O3
|
A:0EW510
|
2.3
|
26.6
|
1.0
|
C20
|
A:0EW510
|
3.2
|
25.9
|
1.0
|
C18
|
A:0EW510
|
3.2
|
26.1
|
1.0
|
OG1
|
A:THR232
|
3.3
|
19.6
|
1.0
|
NH2
|
A:ARG307
|
3.3
|
28.5
|
1.0
|
CG2
|
A:THR232
|
3.4
|
25.8
|
1.0
|
CB
|
A:THR232
|
3.7
|
26.3
|
1.0
|
O
|
A:HOH635
|
3.8
|
43.5
|
1.0
|
CZ
|
A:ARG307
|
3.8
|
31.8
|
1.0
|
CB
|
A:ALA335
|
3.8
|
20.3
|
1.0
|
CA
|
A:THR232
|
3.9
|
26.0
|
1.0
|
NE
|
A:ARG307
|
4.0
|
33.7
|
1.0
|
CA
|
A:GLY11
|
4.1
|
31.9
|
1.0
|
N
|
A:GLY11
|
4.2
|
35.7
|
1.0
|
OE2
|
A:GLU339
|
4.4
|
29.0
|
1.0
|
O
|
A:HOH645
|
4.5
|
37.7
|
1.0
|
C21
|
A:0EW510
|
4.5
|
25.3
|
1.0
|
C17
|
A:0EW510
|
4.6
|
25.7
|
1.0
|
C
|
A:GLY11
|
4.7
|
27.7
|
1.0
|
NH1
|
A:ARG307
|
4.7
|
33.1
|
1.0
|
O
|
A:THR232
|
4.8
|
25.9
|
1.0
|
C
|
A:THR232
|
4.8
|
23.9
|
1.0
|
N
|
A:THR232
|
4.9
|
24.4
|
1.0
|
|
Fluorine binding site 3 out
of 4 in 7n66
Go back to
Fluorine Binding Sites List in 7n66
Fluorine binding site 3 out
of 4 in the Bace-1 in Complex with Ligand 12
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 3 of Bace-1 in Complex with Ligand 12 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F510
b:27.5
occ:1.00
|
F1
|
A:0EW510
|
0.0
|
27.5
|
1.0
|
C14
|
A:0EW510
|
1.3
|
27.4
|
1.0
|
C13
|
A:0EW510
|
2.4
|
26.8
|
1.0
|
C9
|
A:0EW510
|
2.5
|
27.6
|
1.0
|
C7
|
A:0EW510
|
3.0
|
28.4
|
1.0
|
C6
|
A:0EW510
|
3.0
|
29.1
|
1.0
|
CE1
|
A:PHE108
|
3.1
|
27.3
|
1.0
|
C5
|
A:0EW510
|
3.2
|
29.8
|
1.0
|
CD1
|
A:PHE108
|
3.2
|
24.5
|
1.0
|
CE2
|
A:TYR71
|
3.4
|
34.1
|
1.0
|
C1
|
A:DMS507
|
3.4
|
53.2
|
1.0
|
CZ
|
A:TYR71
|
3.6
|
28.6
|
1.0
|
C12
|
A:0EW510
|
3.6
|
26.3
|
1.0
|
C10
|
A:0EW510
|
3.7
|
27.1
|
1.0
|
OH
|
A:TYR71
|
3.7
|
32.8
|
1.0
|
S
|
A:DMS507
|
3.9
|
69.4
|
1.0
|
CD2
|
A:TYR71
|
4.0
|
32.7
|
1.0
|
F
|
A:0EW510
|
4.1
|
29.3
|
1.0
|
C11
|
A:0EW510
|
4.2
|
26.6
|
1.0
|
CE1
|
A:TYR71
|
4.4
|
34.8
|
1.0
|
C4
|
A:0EW510
|
4.4
|
32.9
|
1.0
|
CZ
|
A:PHE108
|
4.4
|
21.9
|
1.0
|
N
|
A:0EW510
|
4.4
|
29.3
|
1.0
|
CG
|
A:PHE108
|
4.5
|
26.2
|
1.0
|
CD1
|
A:ILE118
|
4.7
|
30.1
|
1.0
|
CG
|
A:TYR71
|
4.7
|
37.0
|
1.0
|
CD1
|
A:TYR71
|
4.9
|
33.7
|
1.0
|
O
|
A:DMS507
|
4.9
|
63.5
|
1.0
|
C2
|
A:DMS507
|
5.0
|
59.6
|
1.0
|
O
|
A:HOH606
|
5.0
|
30.2
|
1.0
|
|
Fluorine binding site 4 out
of 4 in 7n66
Go back to
Fluorine Binding Sites List in 7n66
Fluorine binding site 4 out
of 4 in the Bace-1 in Complex with Ligand 12
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 4 of Bace-1 in Complex with Ligand 12 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F510
b:29.3
occ:1.00
|
F
|
A:0EW510
|
0.0
|
29.3
|
1.0
|
C7
|
A:0EW510
|
1.4
|
28.4
|
1.0
|
C6
|
A:0EW510
|
2.4
|
29.1
|
1.0
|
N
|
A:0EW510
|
2.8
|
29.3
|
1.0
|
C5
|
A:0EW510
|
2.9
|
29.8
|
1.0
|
OH
|
A:TYR71
|
3.1
|
32.8
|
1.0
|
O
|
A:HOH702
|
3.3
|
25.4
|
1.0
|
CB
|
A:SER35
|
3.3
|
15.3
|
1.0
|
OD2
|
A:ASP32
|
3.4
|
18.6
|
1.0
|
CE1
|
A:TYR71
|
3.4
|
34.8
|
1.0
|
OG
|
A:SER35
|
3.5
|
19.8
|
1.0
|
O1
|
A:0EW510
|
3.5
|
42.7
|
1.0
|
CZ
|
A:TYR71
|
3.5
|
28.6
|
1.0
|
C9
|
A:0EW510
|
3.7
|
27.6
|
1.0
|
C8
|
A:0EW510
|
3.7
|
32.1
|
1.0
|
F1
|
A:0EW510
|
4.1
|
27.5
|
1.0
|
C4
|
A:0EW510
|
4.1
|
32.9
|
1.0
|
O
|
A:HOH643
|
4.2
|
20.6
|
1.0
|
C2
|
A:0EW510
|
4.3
|
35.4
|
1.0
|
C14
|
A:0EW510
|
4.4
|
27.4
|
1.0
|
CD1
|
A:TYR71
|
4.5
|
33.7
|
1.0
|
S
|
A:0EW510
|
4.5
|
42.8
|
1.0
|
CG
|
A:ASP32
|
4.6
|
19.0
|
1.0
|
N1
|
A:0EW510
|
4.6
|
30.0
|
1.0
|
CE2
|
A:TYR71
|
4.6
|
34.1
|
1.0
|
CA
|
A:SER35
|
4.8
|
19.5
|
1.0
|
C10
|
A:0EW510
|
4.8
|
27.1
|
1.0
|
CG2
|
A:ILE118
|
4.8
|
27.7
|
1.0
|
|
Reference:
F.J.R.Rombouts,
K.I.Kusakabe,
R.Alexander,
N.Austin,
H.Borghys,
M.De Cleyn,
D.Dhuyvetter,
H.J.M.Gijsen,
B.Hrupka,
T.Jacobs,
S.Jerhaoui,
L.Lammens,
L.Leclercq,
K.Tsubone,
T.Ueno,
K.Morimoto,
S.Einaru,
H.Sumiyoshi,
A.Van Den Bergh,
A.Vos,
M.Surkyn,
A.Teisman,
D.Moechars.
Jnj-67569762, A 2-Aminotetrahydropyridine-Based Selective BACE1 Inhibitor Targeting the S3 Pocket: From Discovery to Clinical Candidate. J.Med.Chem. 2021.
ISSN: ISSN 0022-2623
PubMed: 34553934
DOI: 10.1021/ACS.JMEDCHEM.1C00935
Page generated: Fri Aug 2 09:57:19 2024
|