Fluorine in PDB 6ngf: Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine
Enzymatic activity of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine
All present enzymatic activity of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine:
1.14.13.39;
Protein crystallography data
The structure of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine, PDB code: 6ngf
was solved by
H.Li,
T.L.Poulos,
with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:
Resolution Low / High (Å)
|
82.35 /
1.99
|
Space group
|
P 21 21 21
|
Cell size a, b, c (Å), α, β, γ (°)
|
52.330,
121.760,
164.700,
90.00,
90.00,
90.00
|
R / Rfree (%)
|
18.6 /
22.7
|
Other elements in 6ngf:
The structure of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine also contains other interesting chemical elements:
Fluorine Binding Sites:
The binding sites of Fluorine atom in the Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine
(pdb code 6ngf). This binding sites where shown within
5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the
Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine, PDB code: 6ngf:
Jump to Fluorine binding site number:
1;
2;
3;
4;
Fluorine binding site 1 out
of 4 in 6ngf
Go back to
Fluorine Binding Sites List in 6ngf
Fluorine binding site 1 out
of 4 in the Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine
 Mono view
 Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 1 of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F803
b:48.7
occ:1.00
|
F12
|
A:KN4803
|
0.0
|
48.7
|
1.0
|
C12
|
A:KN4803
|
1.3
|
50.4
|
1.0
|
C13
|
A:KN4803
|
2.3
|
50.0
|
1.0
|
C11
|
A:KN4803
|
2.4
|
45.6
|
1.0
|
F13
|
A:KN4803
|
2.7
|
53.4
|
1.0
|
C09
|
A:KN4803
|
2.8
|
33.7
|
1.0
|
OH
|
A:TYR593
|
2.9
|
29.5
|
1.0
|
O
|
A:HOH994
|
3.2
|
45.9
|
1.0
|
C14
|
A:KN4803
|
3.6
|
40.5
|
1.0
|
C16
|
A:KN4803
|
3.6
|
46.6
|
1.0
|
CZ
|
A:TYR593
|
3.7
|
29.0
|
1.0
|
CB
|
A:PRO570
|
3.8
|
16.3
|
1.0
|
CE2
|
A:TYR593
|
3.9
|
32.5
|
1.0
|
CA
|
A:PRO570
|
4.0
|
28.1
|
1.0
|
OH
|
A:TYR567
|
4.0
|
43.4
|
1.0
|
C15
|
A:KN4803
|
4.1
|
50.4
|
1.0
|
CG
|
A:GLN483
|
4.3
|
27.7
|
1.0
|
O
|
A:HOH1035
|
4.3
|
38.4
|
1.0
|
C08
|
A:KN4803
|
4.3
|
34.3
|
1.0
|
CE1
|
A:TYR567
|
4.4
|
23.9
|
1.0
|
O
|
A:HOH982
|
4.6
|
26.9
|
1.0
|
N
|
A:ALA571
|
4.7
|
25.7
|
1.0
|
O
|
A:HOH992
|
4.7
|
58.1
|
1.0
|
CZ
|
A:TYR567
|
4.7
|
31.3
|
1.0
|
CE1
|
A:TYR593
|
4.8
|
24.5
|
1.0
|
C
|
A:PRO570
|
4.8
|
27.5
|
1.0
|
CB
|
A:GLN483
|
4.9
|
23.5
|
1.0
|
C06
|
A:KN4803
|
4.9
|
31.3
|
1.0
|
|
Fluorine binding site 2 out
of 4 in 6ngf
Go back to
Fluorine Binding Sites List in 6ngf
Fluorine binding site 2 out
of 4 in the Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine
 Mono view
 Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 2 of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:F803
b:53.4
occ:1.00
|
F13
|
A:KN4803
|
0.0
|
53.4
|
1.0
|
C13
|
A:KN4803
|
1.3
|
50.0
|
1.0
|
C12
|
A:KN4803
|
2.4
|
50.4
|
1.0
|
C14
|
A:KN4803
|
2.4
|
40.5
|
1.0
|
O
|
A:HOH992
|
2.7
|
58.1
|
1.0
|
F12
|
A:KN4803
|
2.7
|
48.7
|
1.0
|
CD
|
A:ARG486
|
3.0
|
34.6
|
1.0
|
OH
|
A:TYR567
|
3.0
|
43.4
|
1.0
|
NE
|
A:ARG486
|
3.2
|
36.8
|
1.0
|
O
|
A:HOH994
|
3.4
|
45.9
|
1.0
|
CZ
|
A:ARG486
|
3.5
|
30.6
|
1.0
|
NH1
|
A:ARG486
|
3.5
|
28.0
|
1.0
|
C15
|
A:KN4803
|
3.6
|
50.4
|
1.0
|
C11
|
A:KN4803
|
3.6
|
45.6
|
1.0
|
CG
|
A:GLN483
|
3.9
|
27.7
|
1.0
|
OE1
|
A:GLN483
|
4.0
|
46.2
|
1.0
|
CD
|
A:GLN483
|
4.0
|
37.7
|
1.0
|
C16
|
A:KN4803
|
4.1
|
46.6
|
1.0
|
OH
|
A:TYR593
|
4.2
|
29.5
|
1.0
|
CZ
|
A:TYR567
|
4.3
|
31.3
|
1.0
|
NH2
|
A:ARG486
|
4.4
|
33.8
|
1.0
|
CG
|
A:ARG486
|
4.4
|
32.1
|
1.0
|
CB
|
A:GLN483
|
4.5
|
23.5
|
1.0
|
NE2
|
A:GLN483
|
4.7
|
41.9
|
1.0
|
CE1
|
A:TYR567
|
4.7
|
23.9
|
1.0
|
C09
|
A:KN4803
|
4.9
|
33.7
|
1.0
|
C17
|
A:KN4803
|
4.9
|
44.3
|
1.0
|
O
|
A:ILE485
|
4.9
|
22.4
|
1.0
|
|
Fluorine binding site 3 out
of 4 in 6ngf
Go back to
Fluorine Binding Sites List in 6ngf
Fluorine binding site 3 out
of 4 in the Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine
 Mono view
 Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 3 of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:F804
b:71.0
occ:1.00
|
F12
|
B:KN4804
|
0.0
|
71.0
|
1.0
|
C12
|
B:KN4804
|
1.3
|
65.6
|
1.0
|
C13
|
B:KN4804
|
2.4
|
65.5
|
1.0
|
C11
|
B:KN4804
|
2.4
|
59.3
|
1.0
|
F13
|
B:KN4804
|
2.7
|
68.5
|
1.0
|
C09
|
B:KN4804
|
2.8
|
39.6
|
1.0
|
OH
|
B:TYR593
|
3.0
|
30.3
|
1.0
|
O
|
B:HOH909
|
3.4
|
42.3
|
1.0
|
C14
|
B:KN4804
|
3.6
|
60.1
|
1.0
|
C16
|
B:KN4804
|
3.6
|
64.3
|
1.0
|
CZ
|
B:TYR593
|
3.7
|
29.8
|
1.0
|
CB
|
B:PRO570
|
3.9
|
22.6
|
1.0
|
CE2
|
B:TYR593
|
4.0
|
22.1
|
1.0
|
CA
|
B:PRO570
|
4.0
|
27.9
|
1.0
|
OH
|
B:TYR567
|
4.0
|
44.9
|
1.0
|
CG
|
B:GLN483
|
4.1
|
43.2
|
1.0
|
C15
|
B:KN4804
|
4.1
|
64.4
|
1.0
|
C08
|
B:KN4804
|
4.3
|
34.0
|
1.0
|
CE1
|
B:TYR567
|
4.4
|
38.3
|
1.0
|
O
|
B:HOH948
|
4.5
|
29.7
|
1.0
|
O
|
B:HOH1061
|
4.5
|
50.8
|
1.0
|
N
|
B:ALA571
|
4.5
|
24.1
|
1.0
|
O
|
B:HOH970
|
4.6
|
59.2
|
1.0
|
C
|
B:PRO570
|
4.6
|
27.0
|
1.0
|
CB
|
B:GLN483
|
4.6
|
43.9
|
1.0
|
CZ
|
B:TYR567
|
4.8
|
39.1
|
1.0
|
CE1
|
B:TYR593
|
4.8
|
31.3
|
1.0
|
C06
|
B:KN4804
|
4.8
|
32.2
|
1.0
|
|
Fluorine binding site 4 out
of 4 in 6ngf
Go back to
Fluorine Binding Sites List in 6ngf
Fluorine binding site 4 out
of 4 in the Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine
 Mono view
 Stereo pair view
|
A full contact list of Fluorine with other atoms in the F binding
site number 4 of Structure of Human Neuronal Nitric Oxide Synthase R354A/G357D Mutant Heme Domain in Complex with (R)-6-(2,3-Difluoro-5-(2-(1- Methylpyrrolidin-2-Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:F804
b:68.5
occ:1.00
|
F13
|
B:KN4804
|
0.0
|
68.5
|
1.0
|
C13
|
B:KN4804
|
1.3
|
65.5
|
1.0
|
C12
|
B:KN4804
|
2.4
|
65.6
|
1.0
|
C14
|
B:KN4804
|
2.4
|
60.1
|
1.0
|
F12
|
B:KN4804
|
2.7
|
71.0
|
1.0
|
O
|
B:HOH970
|
2.9
|
59.2
|
1.0
|
OH
|
B:TYR567
|
2.9
|
44.9
|
1.0
|
NE
|
B:ARG486
|
3.3
|
46.2
|
1.0
|
CZ
|
B:ARG486
|
3.6
|
47.4
|
1.0
|
CD
|
B:ARG486
|
3.6
|
46.3
|
1.0
|
C15
|
B:KN4804
|
3.6
|
64.4
|
1.0
|
C11
|
B:KN4804
|
3.6
|
59.3
|
1.0
|
CG
|
B:GLN483
|
3.7
|
43.2
|
1.0
|
O
|
B:HOH909
|
3.7
|
42.3
|
1.0
|
CD
|
B:GLN483
|
4.0
|
44.8
|
1.0
|
OE1
|
B:GLN483
|
4.0
|
48.8
|
1.0
|
NH1
|
B:ARG486
|
4.0
|
35.3
|
1.0
|
NH2
|
B:ARG486
|
4.1
|
55.4
|
1.0
|
CB
|
B:GLN483
|
4.1
|
43.9
|
1.0
|
C16
|
B:KN4804
|
4.1
|
64.3
|
1.0
|
CZ
|
B:TYR567
|
4.2
|
39.1
|
1.0
|
OH
|
B:TYR593
|
4.2
|
30.3
|
1.0
|
CG
|
B:ARG486
|
4.3
|
44.2
|
1.0
|
O
|
B:ILE485
|
4.7
|
32.5
|
1.0
|
CE1
|
B:TYR567
|
4.7
|
38.3
|
1.0
|
NE2
|
B:GLN483
|
4.8
|
43.9
|
1.0
|
C09
|
B:KN4804
|
4.8
|
39.6
|
1.0
|
C17
|
B:KN4804
|
4.9
|
66.7
|
1.0
|
|
Reference:
H.T.Do,
H.Li,
G.Chreifi,
T.L.Poulos,
R.B.Silverman.
Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having A 2-Aminopyridine Scaffold. J. Med. Chem. V. 62 2690 2019.
ISSN: ISSN 1520-4804
PubMed: 30802056
DOI: 10.1021/ACS.JMEDCHEM.8B02032
Page generated: Sun Dec 13 13:00:03 2020
|