Fluorine in PDB 4xv2: B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
Enzymatic activity of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
All present enzymatic activity of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib:
2.7.11.1;
Protein crystallography data
The structure of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib, PDB code: 4xv2
was solved by
Y.Zhang,
C.Zhang,
with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:
Resolution Low / High (Å)
|
54.87 /
2.50
|
Space group
|
P 21 21 21
|
Cell size a, b, c (Å), α, β, γ (°)
|
53.689,
105.666,
109.731,
90.00,
90.00,
90.00
|
R / Rfree (%)
|
21.2 /
24.4
|
Fluorine Binding Sites:
The binding sites of Fluorine atom in the B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
(pdb code 4xv2). This binding sites where shown within
5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the
B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib, PDB code: 4xv2:
Jump to Fluorine binding site number:
1;
2;
3;
4;
5;
6;
Fluorine binding site 1 out
of 6 in 4xv2
Go back to
Fluorine Binding Sites List in 4xv2
Fluorine binding site 1 out
of 6 in the B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 1 of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F801
b:37.5
occ:1.00
|
F39
|
A:P06801
|
0.0
|
37.5
|
1.0
|
C32
|
A:P06801
|
1.3
|
33.9
|
1.0
|
C31
|
A:P06801
|
2.3
|
32.5
|
1.0
|
C30
|
A:P06801
|
2.4
|
33.5
|
1.0
|
N40
|
A:P06801
|
2.7
|
28.4
|
1.0
|
C16
|
A:P06801
|
2.8
|
33.3
|
1.0
|
N15
|
A:P06801
|
2.9
|
34.3
|
1.0
|
O
|
A:HOH913
|
3.0
|
31.0
|
1.0
|
N
|
A:ASP594
|
3.1
|
38.3
|
1.0
|
CA
|
A:ASP594
|
3.4
|
38.5
|
1.0
|
CB
|
A:ASP594
|
3.4
|
41.0
|
1.0
|
C33
|
A:P06801
|
3.6
|
29.5
|
1.0
|
C35
|
A:P06801
|
3.6
|
31.7
|
1.0
|
CE2
|
A:PHE583
|
3.9
|
43.4
|
1.0
|
C12
|
A:P06801
|
3.9
|
35.1
|
1.0
|
C
|
A:GLY593
|
3.9
|
37.8
|
1.0
|
CZ
|
A:PHE583
|
3.9
|
39.2
|
1.0
|
OD1
|
A:ASP594
|
4.0
|
50.0
|
1.0
|
C14
|
A:P06801
|
4.0
|
37.0
|
1.0
|
CG
|
A:ASP594
|
4.0
|
49.2
|
1.0
|
C37
|
A:P06801
|
4.1
|
27.3
|
1.0
|
CA
|
A:GLY593
|
4.2
|
38.5
|
1.0
|
S42
|
A:P06801
|
4.3
|
33.8
|
1.0
|
NZ
|
A:LYS483
|
4.3
|
42.6
|
1.0
|
CD2
|
A:LEU514
|
4.4
|
30.7
|
1.0
|
C22
|
A:P06801
|
4.6
|
38.1
|
1.0
|
C4
|
A:P06801
|
4.8
|
36.2
|
1.0
|
S13
|
A:P06801
|
4.8
|
39.5
|
1.0
|
C2
|
A:P06801
|
4.8
|
36.7
|
1.0
|
CE
|
A:LYS483
|
4.8
|
41.7
|
1.0
|
O
|
A:GLY593
|
4.8
|
34.3
|
1.0
|
C
|
A:ASP594
|
4.9
|
41.4
|
1.0
|
O54
|
A:P06801
|
4.9
|
36.3
|
1.0
|
O55
|
A:P06801
|
4.9
|
34.5
|
1.0
|
C17
|
A:P06801
|
5.0
|
38.8
|
1.0
|
OD2
|
A:ASP594
|
5.0
|
52.6
|
1.0
|
|
Fluorine binding site 2 out
of 6 in 4xv2
Go back to
Fluorine Binding Sites List in 4xv2
Fluorine binding site 2 out
of 6 in the B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 2 of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F801
b:43.3
occ:1.00
|
F52
|
A:P06801
|
0.0
|
43.3
|
1.0
|
C49
|
A:P06801
|
1.3
|
39.4
|
1.0
|
C50
|
A:P06801
|
2.4
|
38.8
|
1.0
|
C43
|
A:P06801
|
2.4
|
38.5
|
1.0
|
O55
|
A:P06801
|
2.7
|
34.5
|
1.0
|
S42
|
A:P06801
|
2.9
|
33.8
|
1.0
|
N40
|
A:P06801
|
3.1
|
28.4
|
1.0
|
CA
|
A:GLY593
|
3.1
|
38.5
|
1.0
|
N
|
A:ASP594
|
3.3
|
38.3
|
1.0
|
C
|
A:GLY593
|
3.5
|
37.8
|
1.0
|
C47
|
A:P06801
|
3.6
|
38.8
|
1.0
|
C46
|
A:P06801
|
3.6
|
37.2
|
1.0
|
CE1
|
A:PHE595
|
3.6
|
52.2
|
1.0
|
CD1
|
A:PHE595
|
3.7
|
53.2
|
1.0
|
CZ
|
A:PHE595
|
3.9
|
53.0
|
1.0
|
O
|
A:ILE592
|
4.0
|
42.4
|
1.0
|
CG
|
A:PHE595
|
4.0
|
52.9
|
1.0
|
C44
|
A:P06801
|
4.1
|
37.8
|
1.0
|
N
|
A:PHE595
|
4.2
|
42.4
|
1.0
|
C31
|
A:P06801
|
4.2
|
32.5
|
1.0
|
CE2
|
A:PHE595
|
4.3
|
55.0
|
1.0
|
CD2
|
A:LEU514
|
4.3
|
30.7
|
1.0
|
CD2
|
A:PHE595
|
4.3
|
55.4
|
1.0
|
CB
|
A:LEU514
|
4.3
|
31.1
|
1.0
|
N
|
A:GLY593
|
4.3
|
39.3
|
1.0
|
O54
|
A:P06801
|
4.3
|
36.3
|
1.0
|
CA
|
A:ASP594
|
4.4
|
38.5
|
1.0
|
O
|
A:GLY593
|
4.5
|
34.3
|
1.0
|
C
|
A:ILE592
|
4.6
|
38.8
|
1.0
|
CD2
|
A:LEU505
|
4.7
|
38.3
|
1.0
|
F53
|
A:P06801
|
4.8
|
34.7
|
1.0
|
C
|
A:ASP594
|
4.8
|
41.4
|
1.0
|
CB
|
A:PHE595
|
4.8
|
48.9
|
1.0
|
CG
|
A:LEU514
|
4.9
|
31.1
|
1.0
|
C33
|
A:P06801
|
4.9
|
29.5
|
1.0
|
|
Fluorine binding site 3 out
of 6 in 4xv2
Go back to
Fluorine Binding Sites List in 4xv2
Fluorine binding site 3 out
of 6 in the B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 3 of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F801
b:34.7
occ:1.00
|
F53
|
A:P06801
|
0.0
|
34.7
|
1.0
|
C46
|
A:P06801
|
1.3
|
37.2
|
1.0
|
C44
|
A:P06801
|
2.3
|
37.8
|
1.0
|
C43
|
A:P06801
|
2.4
|
38.5
|
1.0
|
O54
|
A:P06801
|
2.7
|
36.3
|
1.0
|
S42
|
A:P06801
|
3.1
|
33.8
|
1.0
|
CG2
|
A:ILE527
|
3.1
|
38.9
|
1.0
|
CD1
|
A:LEU505
|
3.3
|
44.1
|
1.0
|
C33
|
A:P06801
|
3.5
|
29.5
|
1.0
|
C47
|
A:P06801
|
3.6
|
38.8
|
1.0
|
C49
|
A:P06801
|
3.6
|
39.4
|
1.0
|
CG2
|
A:THR529
|
3.6
|
28.1
|
1.0
|
CB
|
A:ILE527
|
4.1
|
37.6
|
1.0
|
C50
|
A:P06801
|
4.1
|
38.8
|
1.0
|
N40
|
A:P06801
|
4.2
|
28.4
|
1.0
|
CD1
|
A:ILE527
|
4.2
|
39.9
|
1.0
|
O55
|
A:P06801
|
4.2
|
34.5
|
1.0
|
C31
|
A:P06801
|
4.3
|
32.5
|
1.0
|
CG
|
A:LEU505
|
4.4
|
42.5
|
1.0
|
CD2
|
A:LEU505
|
4.4
|
38.3
|
1.0
|
C37
|
A:P06801
|
4.5
|
27.3
|
1.0
|
CG1
|
A:ILE527
|
4.7
|
39.6
|
1.0
|
F52
|
A:P06801
|
4.8
|
43.3
|
1.0
|
CB
|
A:LEU505
|
5.0
|
41.3
|
1.0
|
|
Fluorine binding site 4 out
of 6 in 4xv2
Go back to
Fluorine Binding Sites List in 4xv2
Fluorine binding site 4 out
of 6 in the B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 4 of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:F801
b:44.6
occ:1.00
|
F39
|
B:P06801
|
0.0
|
44.6
|
1.0
|
C32
|
B:P06801
|
1.3
|
43.4
|
1.0
|
C31
|
B:P06801
|
2.3
|
42.6
|
1.0
|
C30
|
B:P06801
|
2.4
|
42.7
|
1.0
|
N40
|
B:P06801
|
2.7
|
40.8
|
1.0
|
C16
|
B:P06801
|
2.8
|
44.1
|
1.0
|
O
|
B:HOH913
|
2.8
|
49.0
|
1.0
|
N15
|
B:P06801
|
2.9
|
46.9
|
1.0
|
N
|
B:ASP594
|
3.1
|
43.8
|
1.0
|
CB
|
B:ASP594
|
3.4
|
46.0
|
1.0
|
CA
|
B:ASP594
|
3.4
|
45.1
|
1.0
|
C33
|
B:P06801
|
3.6
|
42.2
|
1.0
|
C35
|
B:P06801
|
3.6
|
42.7
|
1.0
|
CZ
|
B:PHE583
|
3.8
|
51.9
|
1.0
|
C12
|
B:P06801
|
3.8
|
44.5
|
1.0
|
C14
|
B:P06801
|
3.9
|
48.2
|
1.0
|
C
|
B:GLY593
|
4.0
|
38.9
|
1.0
|
CE2
|
B:PHE583
|
4.0
|
51.1
|
1.0
|
C37
|
B:P06801
|
4.1
|
41.8
|
1.0
|
CG
|
B:ASP594
|
4.1
|
50.3
|
1.0
|
NZ
|
B:LYS483
|
4.1
|
49.4
|
1.0
|
CA
|
B:GLY593
|
4.3
|
32.4
|
1.0
|
OD1
|
B:ASP594
|
4.3
|
51.5
|
1.0
|
S42
|
B:P06801
|
4.3
|
46.3
|
1.0
|
CD2
|
B:LEU514
|
4.4
|
34.0
|
1.0
|
C26
|
B:P06801
|
4.7
|
44.7
|
1.0
|
C2
|
B:P06801
|
4.7
|
45.8
|
1.0
|
CE
|
B:LYS483
|
4.7
|
50.7
|
1.0
|
S13
|
B:P06801
|
4.7
|
48.1
|
1.0
|
C4
|
B:P06801
|
4.7
|
43.9
|
1.0
|
O55
|
B:P06801
|
4.9
|
47.1
|
1.0
|
O54
|
B:P06801
|
4.9
|
44.8
|
1.0
|
C17
|
B:P06801
|
4.9
|
47.9
|
1.0
|
O
|
B:GLY593
|
4.9
|
38.6
|
1.0
|
C
|
B:ASP594
|
4.9
|
47.8
|
1.0
|
OD2
|
B:ASP594
|
5.0
|
53.5
|
1.0
|
CE1
|
B:PHE583
|
5.0
|
51.9
|
1.0
|
|
Fluorine binding site 5 out
of 6 in 4xv2
Go back to
Fluorine Binding Sites List in 4xv2
Fluorine binding site 5 out
of 6 in the B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 5 of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:F801
b:50.0
occ:1.00
|
F52
|
B:P06801
|
0.0
|
50.0
|
1.0
|
C49
|
B:P06801
|
1.3
|
48.3
|
1.0
|
C50
|
B:P06801
|
2.4
|
48.3
|
1.0
|
C43
|
B:P06801
|
2.4
|
47.5
|
1.0
|
O55
|
B:P06801
|
2.8
|
47.1
|
1.0
|
S42
|
B:P06801
|
3.0
|
46.3
|
1.0
|
CA
|
B:GLY593
|
3.1
|
32.4
|
1.0
|
N40
|
B:P06801
|
3.2
|
40.8
|
1.0
|
N
|
B:ASP594
|
3.4
|
43.8
|
1.0
|
CE1
|
B:PHE595
|
3.5
|
66.3
|
1.0
|
C
|
B:GLY593
|
3.6
|
38.9
|
1.0
|
C47
|
B:P06801
|
3.6
|
47.7
|
1.0
|
C46
|
B:P06801
|
3.6
|
47.2
|
1.0
|
CD1
|
B:PHE595
|
3.7
|
66.5
|
1.0
|
CZ
|
B:PHE595
|
3.8
|
65.9
|
1.0
|
O
|
B:ILE592
|
3.9
|
32.6
|
1.0
|
CD2
|
B:LEU514
|
4.0
|
34.0
|
1.0
|
CG
|
B:PHE595
|
4.1
|
64.7
|
1.0
|
C44
|
B:P06801
|
4.1
|
47.4
|
1.0
|
CB
|
B:LEU514
|
4.2
|
35.3
|
1.0
|
CE2
|
B:PHE595
|
4.2
|
67.3
|
1.0
|
N
|
B:GLY593
|
4.3
|
33.0
|
1.0
|
CD2
|
B:PHE595
|
4.3
|
67.0
|
1.0
|
C31
|
B:P06801
|
4.3
|
42.6
|
1.0
|
N
|
B:PHE595
|
4.4
|
49.6
|
1.0
|
O54
|
B:P06801
|
4.4
|
44.8
|
1.0
|
CD2
|
B:LEU505
|
4.5
|
47.9
|
1.0
|
C
|
B:ILE592
|
4.5
|
33.4
|
1.0
|
O
|
B:GLY593
|
4.5
|
38.6
|
1.0
|
CA
|
B:ASP594
|
4.5
|
45.1
|
1.0
|
CG
|
B:LEU514
|
4.7
|
37.1
|
1.0
|
F53
|
B:P06801
|
4.8
|
48.5
|
1.0
|
C
|
B:ASP594
|
4.9
|
47.8
|
1.0
|
C33
|
B:P06801
|
5.0
|
42.2
|
1.0
|
CB
|
B:PHE595
|
5.0
|
60.5
|
1.0
|
O
|
B:LEU514
|
5.0
|
38.1
|
1.0
|
|
Fluorine binding site 6 out
of 6 in 4xv2
Go back to
Fluorine Binding Sites List in 4xv2
Fluorine binding site 6 out
of 6 in the B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib
Mono view
Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 6 of B-Raf Kinase V600E Oncogenic Mutant in Complex with Dabrafenib within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:F801
b:48.5
occ:1.00
|
F53
|
B:P06801
|
0.0
|
48.5
|
1.0
|
C46
|
B:P06801
|
1.3
|
47.2
|
1.0
|
C44
|
B:P06801
|
2.3
|
47.4
|
1.0
|
C43
|
B:P06801
|
2.4
|
47.5
|
1.0
|
O54
|
B:P06801
|
2.6
|
44.8
|
1.0
|
S42
|
B:P06801
|
3.0
|
46.3
|
1.0
|
CG2
|
B:ILE527
|
3.2
|
42.2
|
1.0
|
CD1
|
B:LEU505
|
3.3
|
51.1
|
1.0
|
C33
|
B:P06801
|
3.5
|
42.2
|
1.0
|
CG2
|
B:THR529
|
3.6
|
43.1
|
1.0
|
C47
|
B:P06801
|
3.6
|
47.7
|
1.0
|
C49
|
B:P06801
|
3.6
|
48.3
|
1.0
|
CB
|
B:ILE527
|
4.0
|
47.1
|
1.0
|
N40
|
B:P06801
|
4.1
|
40.8
|
1.0
|
C50
|
B:P06801
|
4.1
|
48.3
|
1.0
|
O55
|
B:P06801
|
4.2
|
47.1
|
1.0
|
C31
|
B:P06801
|
4.2
|
42.6
|
1.0
|
CD1
|
B:ILE527
|
4.2
|
46.1
|
1.0
|
CD2
|
B:LEU505
|
4.3
|
47.9
|
1.0
|
CG
|
B:LEU505
|
4.4
|
50.8
|
1.0
|
C37
|
B:P06801
|
4.5
|
41.8
|
1.0
|
CG1
|
B:ILE527
|
4.7
|
47.4
|
1.0
|
F52
|
B:P06801
|
4.8
|
50.0
|
1.0
|
|
Reference:
C.Zhang,
W.Spevak,
Y.Zhang,
E.A.Burton,
Y.Ma,
G.Habets,
J.Zhang,
J.Lin,
T.Ewing,
B.Matusow,
G.Tsang,
A.Marimuthu,
H.Cho,
G.Wu,
W.Wang,
D.Fong,
H.Nguyen,
S.Shi,
P.Womack,
M.Nespi,
R.Shellooe,
H.Carias,
B.Powell,
E.Light,
L.Sanftner,
J.Walters,
J.Tsai,
B.L.West,
G.Visor,
H.Rezaei,
P.S.Lin,
K.Nolop,
P.N.Ibrahim,
P.Hirth,
G.Bollag.
Raf Inhibitors That Evade Paradoxical Mapk Pathway Activation. Nature V. 526 583 2015.
ISSN: ESSN 1476-4687
PubMed: 26466569
DOI: 10.1038/NATURE14982
Page generated: Thu Aug 1 06:48:33 2024
|