Fluorine in PDB 5ygx: Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide

Enzymatic activity of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide

All present enzymatic activity of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide:
3.4.23.46;

Protein crystallography data

The structure of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide, PDB code: 5ygx was solved by K.Nakahara, K.Fuchino, K.Komano, N.Asada, G.Tadano, T.Hasegawa, T.Yamamoto, Y.Sako, M.Ogawa, C.Unemura, M.Hosono, G.Sakaguchi, S.Ando, S.Ohnishi, Y.Kido, T.Fukushima, D.Dhuyvetter, H.Borghys, H.Gijsen, Y.Yamano, Y.Iso, K.Kusakabe, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 20.00 / 2.20
Space group P 61 2 2
Cell size a, b, c (Å), α, β, γ (°) 101.550, 101.550, 170.811, 90.00, 90.00, 120.00
R / Rfree (%) 17.8 / 20.7

Other elements in 5ygx:

The structure of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide also contains other interesting chemical elements:

Iodine (I) 2 atoms

Fluorine Binding Sites:

The binding sites of Fluorine atom in the Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide (pdb code 5ygx). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 5 binding sites of Fluorine where determined in the Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide, PDB code: 5ygx:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5;

Fluorine binding site 1 out of 5 in 5ygx

Go back to Fluorine Binding Sites List in 5ygx
Fluorine binding site 1 out of 5 in the Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F509

b:25.6
occ:1.00
F4 A:0B5509 0.0 25.6 1.0
C18 A:0B5509 1.3 25.2 1.0
C17 A:0B5509 2.3 24.4 1.0
C7 A:0B5509 2.5 25.0 1.0
C1 A:0B5509 3.0 25.4 1.0
C A:0B5509 3.0 24.0 1.0
CE1 A:PHE108 3.2 23.9 1.0
C2 A:0B5509 3.2 26.0 1.0
CD1 A:PHE108 3.3 24.6 1.0
CE2 A:TYR71 3.4 43.7 1.0
CZ A:TYR71 3.5 42.7 1.0
C16 A:0B5509 3.6 24.7 1.0
C8 A:0B5509 3.7 24.4 1.0
OH A:TYR71 3.7 48.5 1.0
O A:HOH802 3.8 48.1 1.0
CD2 A:TYR71 4.0 43.5 1.0
CD1 A:ILE118 4.0 25.5 1.0
CE1 A:TYR71 4.1 43.2 1.0
F A:0B5509 4.1 27.6 1.0
C9 A:0B5509 4.1 25.4 1.0
C3 A:0B5509 4.2 27.1 1.0
N1 A:0B5509 4.5 23.9 1.0
CZ A:PHE108 4.5 23.8 1.0
CG A:TYR71 4.5 44.1 1.0
CD1 A:TYR71 4.6 44.5 1.0
CG A:PHE108 4.6 25.0 1.0
F1 A:0B5509 4.7 31.5 1.0

Fluorine binding site 2 out of 5 in 5ygx

Go back to Fluorine Binding Sites List in 5ygx
Fluorine binding site 2 out of 5 in the Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F509

b:31.5
occ:1.00
F1 A:0B5509 0.0 31.5 1.0
C4 A:0B5509 1.3 30.1 1.0
F2 A:0B5509 2.2 30.6 1.0
C3 A:0B5509 2.3 27.1 1.0
C5 A:0B5509 2.4 29.3 1.0
C2 A:0B5509 2.9 26.0 1.0
O A:HOH628 3.3 53.4 1.0
F A:0B5509 3.3 27.6 1.0
O A:0B5509 3.6 26.2 1.0
CD1 A:TYR71 3.6 44.5 1.0
CG A:TYR71 3.9 44.1 1.0
CB A:TYR71 4.0 45.2 1.0
C1 A:0B5509 4.3 25.4 1.0
CE1 A:TYR71 4.4 43.2 1.0
C7 A:0B5509 4.7 25.0 1.0
O A:HOH802 4.7 48.1 1.0
F4 A:0B5509 4.7 25.6 1.0
C6 A:0B5509 4.7 24.1 1.0
CD2 A:TYR71 4.8 43.5 1.0
C18 A:0B5509 4.9 25.2 1.0
O A:HOH712 4.9 37.1 1.0

Fluorine binding site 3 out of 5 in 5ygx

Go back to Fluorine Binding Sites List in 5ygx
Fluorine binding site 3 out of 5 in the Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F509

b:30.6
occ:1.00
F2 A:0B5509 0.0 30.6 1.0
C4 A:0B5509 1.3 30.1 1.0
F1 A:0B5509 2.2 31.5 1.0
C5 A:0B5509 2.3 29.3 1.0
C3 A:0B5509 2.3 27.1 1.0
O A:0B5509 2.7 26.2 1.0
O A:HOH712 3.5 37.1 1.0
O A:HOH748 3.7 36.3 1.0
C2 A:0B5509 3.7 26.0 1.0
C6 A:0B5509 4.2 24.1 1.0
F A:0B5509 4.2 27.6 1.0
O A:HOH628 4.5 53.4 1.0
OG1 A:THR231 4.5 25.5 1.0
C1 A:0B5509 4.8 25.4 1.0
O A:HOH763 4.9 37.7 1.0
N1 A:0B5509 4.9 23.9 1.0
N A:0B5509 4.9 22.9 1.0

Fluorine binding site 4 out of 5 in 5ygx

Go back to Fluorine Binding Sites List in 5ygx
Fluorine binding site 4 out of 5 in the Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F509

b:27.6
occ:1.00
F A:0B5509 0.0 27.6 1.0
C2 A:0B5509 1.4 26.0 1.0
C1 A:0B5509 2.3 25.4 1.0
C3 A:0B5509 2.4 27.1 1.0
C A:0B5509 2.7 24.0 1.0
N1 A:0B5509 2.9 23.9 1.0
O A:0B5509 3.0 26.2 1.0
C4 A:0B5509 3.0 30.1 1.0
C5 A:0B5509 3.0 29.3 1.0
CE1 A:TYR71 3.0 43.2 1.0
C6 A:0B5509 3.1 24.1 1.0
F1 A:0B5509 3.3 31.5 1.0
CD1 A:TYR71 3.5 44.5 1.0
C7 A:0B5509 3.7 25.0 1.0
C2 A:GOL504 3.8 68.6 1.0
CZ A:TYR71 3.8 42.7 1.0
O2 A:GOL504 4.1 61.7 1.0
F4 A:0B5509 4.1 25.6 1.0
OH A:TYR71 4.2 48.5 1.0
N A:0B5509 4.2 22.9 1.0
F2 A:0B5509 4.2 30.6 1.0
C18 A:0B5509 4.4 25.2 1.0
O1 A:GOL504 4.4 61.5 1.0
O3 A:GOL504 4.5 74.5 1.0
CG A:TYR71 4.6 44.1 1.0
C1 A:GOL504 4.6 65.4 1.0
CB A:SER35 4.7 20.0 1.0
C8 A:0B5509 4.7 24.4 1.0
OD2 A:ASP32 4.8 22.0 1.0
C3 A:GOL504 4.8 72.6 1.0
CE2 A:TYR71 4.8 43.7 1.0
O A:GLY34 4.9 22.7 1.0

Fluorine binding site 5 out of 5 in 5ygx

Go back to Fluorine Binding Sites List in 5ygx
Fluorine binding site 5 out of 5 in the Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Structure of BACE1 in Complex with N-(3-((4R,5R,6S)-2-Amino-6-(1,1- Difluoroethyl)-5-Fluoro-4-Methyl-5,6-Dihydro-4H-1,3-Oxazin-4-Yl)-4- Fluorophenyl)-5-(Fluoromethoxy)Pyrazine-2-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F509

b:32.9
occ:1.00
F3 A:0B5509 0.0 32.9 1.0
C14 A:0B5509 1.4 29.9 1.0
O1 A:0B5509 2.3 28.0 1.0
O A:HOH739 2.9 40.8 1.0
C13 A:0B5509 3.0 27.3 1.0
N A:GLY13 3.1 24.5 1.0
N4 A:0B5509 3.1 28.2 1.0
CA A:GLY13 3.4 24.1 1.0
N A:GLY11 3.5 31.7 1.0
N A:GLN12 3.7 26.2 1.0
CE2 A:TYR14 3.8 24.5 1.0
CA A:GLY11 3.8 29.1 1.0
C A:GLY11 4.0 26.6 1.0
O A:LYS9 4.2 33.7 1.0
C12 A:0B5509 4.2 26.6 1.0
C A:GLY13 4.2 24.0 1.0
C A:GLN12 4.2 27.3 1.0
CD2 A:TYR14 4.3 23.2 1.0
NH2 A:ARG307 4.3 30.6 1.0
C15 A:0B5509 4.3 26.9 1.0
O A:GLY13 4.5 25.1 1.0
OG1 A:THR232 4.5 26.3 1.0
C A:SER10 4.6 34.0 1.0
CA A:GLN12 4.6 26.7 1.0
CZ A:TYR14 4.6 25.6 1.0
OE1 A:GLU339 4.6 31.1 1.0
CB A:ALA335 4.7 22.2 1.0
OH A:TYR14 4.8 26.6 1.0
O A:GLY11 4.8 26.3 1.0
CA A:SER10 4.9 36.0 1.0

Reference:

K.Nakahara, K.Fuchino, K.Komano, N.Asada, G.Tadano, T.Hasegawa, T.Yamamoto, Y.Sako, M.Ogawa, C.Unemura, M.Hosono, H.Ito, G.Sakaguchi, S.Ando, S.Ohnishi, Y.Kido, T.Fukushima, D.Dhuyvetter, H.Borghys, H.J.M.Gijsen, Y.Yamano, Y.Iso, K.I.Kusakabe. Discovery of Potent and Centrally Active 6-Substituted 5-Fluoro-1,3-Dihydro-Oxazine Beta-Secretase (BACE1) Inhibitors Via Active Conformation Stabilization J. Med. Chem. V. 61 5525 2018.
ISSN: ISSN 1520-4804
PubMed: 29775538
DOI: 10.1021/ACS.JMEDCHEM.8B00011
Page generated: Sun Dec 13 12:43:28 2020

Last articles

Zn in 7VD8
Zn in 7V1R
Zn in 7V1Q
Zn in 7VPF
Zn in 7T85
Zn in 7T5F
Zn in 7NF9
Zn in 7M4M
Zn in 7M4O
Zn in 7M4N
© Copyright 2008-2020 by atomistry.com
Home   |    Site Map   |    Copyright   |    Contact us   |    Privacy