Atomistry » Fluorine » PDB 5he2-5hu1 » 5hu1
Atomistry »
  Fluorine »
    PDB 5he2-5hu1 »
      5hu1 »

Fluorine in PDB 5hu1: BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide

Enzymatic activity of BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide

All present enzymatic activity of BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide:
3.4.23.46;

Protein crystallography data

The structure of BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide, PDB code: 5hu1 was solved by P.Orth, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 45.33 / 1.50
Space group P 21 21 21
Cell size a, b, c (Å), α, β, γ (°) 87.050, 90.200, 131.360, 90.00, 90.00, 90.00
R / Rfree (%) 18.5 / 20.1

Fluorine Binding Sites:

The binding sites of Fluorine atom in the BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide (pdb code 5hu1). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide, PDB code: 5hu1:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in 5hu1

Go back to Fluorine Binding Sites List in 5hu1
Fluorine binding site 1 out of 4 in the BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F501

b:19.0
occ:1.00
 F18 A:66F501 0.0 19.0 1.0
C17 A:66F501 1.4 16.9 1.0
C1 A:66F501 2.4 14.6 1.0
C16 A:66F501 2.4 16.2 1.0
C2 A:66F501 2.9 14.8 1.0
C4 A:66F501 3.0 15.9 1.0
C3 A:66F501 3.0 15.6 1.0
CD2 A:TYR132 3.2 25.4 1.0
CE1 A:PHE169 3.3 22.1 1.0
CE2 A:TYR132 3.3 24.9 1.0
CD1 A:PHE169 3.5 22.2 1.0
C13 A:66F501 3.6 13.7 1.0
C15 A:66F501 3.6 17.3 1.0
O12 A:66F501 3.7 19.2 1.0
S5 A:66F501 4.0 20.2 1.0
C14 A:66F501 4.1 15.8 1.0
CG A:TYR132 4.1 25.8 1.0
CZ A:TYR132 4.2 31.1 1.0
CD1 A:ILE179 4.3 18.0 1.0
N8 A:66F501 4.3 13.2 1.0
CZ A:PHE169 4.5 20.7 1.0
CB A:TYR132 4.8 26.2 1.0
CG A:PHE169 4.9 21.5 1.0
CD1 A:TYR132 4.9 26.9 1.0
OH A:TYR132 4.9 32.6 1.0
O A:HOH658 4.9 26.8 1.0
CE1 A:TYR132 5.0 26.4 1.0

Fluorine binding site 2 out of 4 in 5hu1

Go back to Fluorine Binding Sites List in 5hu1
Fluorine binding site 2 out of 4 in the BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F501

b:16.7
occ:1.00
 F28 A:66F501 0.0 16.7 1.0
C21 A:66F501 1.3 13.8 1.0
C22 A:66F501 2.4 13.4 1.0
C20 A:66F501 2.4 15.6 1.0
O A:SER71 2.8 16.7 1.0
CB A:ALA396 3.5 13.3 1.0
N23 A:66F501 3.6 14.5 1.0
C A:SER71 3.6 14.9 1.0
OG1 A:THR293 3.6 14.5 1.0
C25 A:66F501 3.6 16.3 1.0
CA A:GLY74 3.7 12.8 1.0
CA A:SER71 3.8 12.7 1.0
N A:GLY74 3.8 13.3 1.0
CA A:THR293 3.8 11.6 1.0
O A:THR292 4.0 13.2 1.0
C24 A:66F501 4.1 15.2 1.0
N A:THR293 4.1 12.3 1.0
O A:LYS70 4.1 13.9 1.0
C A:THR292 4.2 14.3 1.0
O A:SER290 4.2 12.5 1.0
CB A:THR293 4.3 14.4 1.0
O A:HOH785 4.6 14.4 1.0
CB A:SER71 4.6 14.9 1.0
C A:GLN73 4.7 18.5 1.0
C A:GLY74 4.8 13.6 1.0
N A:GLY72 4.8 15.1 1.0
N A:SER71 4.8 13.1 1.0
CA A:ALA396 4.9 11.5 1.0
C A:LYS70 4.9 14.4 1.0
N A:GLN73 4.9 16.3 1.0
CD2 A:TYR75 4.9 13.2 1.0
CG2 A:THR293 4.9 13.2 1.0
N A:THR292 5.0 12.1 1.0
C A:GLY72 5.0 19.6 1.0
N A:TYR75 5.0 11.4 1.0

Fluorine binding site 3 out of 4 in 5hu1

Go back to Fluorine Binding Sites List in 5hu1
Fluorine binding site 3 out of 4 in the BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F501

b:20.2
occ:1.00
 F18 B:66F501 0.0 20.2 1.0
C17 B:66F501 1.3 19.4 1.0
C16 B:66F501 2.3 18.1 1.0
C1 B:66F501 2.4 15.4 1.0
C2 B:66F501 2.9 14.5 1.0
C3 B:66F501 3.0 16.1 1.0
C4 B:66F501 3.0 16.4 1.0
CE1 B:PHE169 3.3 19.0 1.0
CD2 B:TYR132 3.4 26.5 1.0
CD1 B:PHE169 3.5 19.3 1.0
CE2 B:TYR132 3.5 26.8 1.0
C13 B:66F501 3.6 14.7 1.0
C15 B:66F501 3.6 18.1 1.0
O12 B:66F501 3.8 19.5 1.0
C14 B:66F501 4.1 16.0 1.0
S5 B:66F501 4.1 20.1 1.0
CD1 B:ILE179 4.2 19.0 1.0
N8 B:66F501 4.3 14.8 1.0
CG B:TYR132 4.4 26.0 1.0
CZ B:TYR132 4.5 33.0 1.0
CZ B:PHE169 4.6 17.3 1.0
CD1 B:TRP137 4.7 21.2 1.0
CG B:PHE169 4.8 17.1 1.0
O B:GLY135 4.8 35.8 1.0
O B:HOH644 4.9 23.6 1.0
NE1 B:TRP137 5.0 19.9 1.0
CB B:TYR132 5.0 24.5 1.0

Fluorine binding site 4 out of 4 in 5hu1

Go back to Fluorine Binding Sites List in 5hu1
Fluorine binding site 4 out of 4 in the BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of BACE1 in Complex with (R)-N-(3-(3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6- Dihydro-2H-1,2,4-Thiadiazin-5-Yl)-4-Fluorophenyl)-5- Fluoropicolinamide within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F501

b:17.0
occ:1.00
 F28 B:66F501 0.0 17.0 1.0
C21 B:66F501 1.4 15.5 1.0
C22 B:66F501 2.4 13.7 1.0
C20 B:66F501 2.4 17.0 1.0
O B:SER71 2.9 15.4 1.0
CB B:ALA396 3.5 12.5 1.0
N23 B:66F501 3.6 14.1 1.0
CA B:GLY74 3.6 14.0 1.0
OG1 B:THR293 3.7 15.1 1.0
C25 B:66F501 3.7 17.8 1.0
C B:SER71 3.7 14.6 1.0
N B:GLY74 3.7 14.8 1.0
CA B:SER71 3.9 13.3 1.0
CA B:THR293 3.9 12.2 1.0
O B:THR292 4.0 12.6 1.0
C24 B:66F501 4.0 15.2 1.0
N B:THR293 4.1 12.2 1.0
O B:SER290 4.1 13.5 1.0
C B:THR292 4.1 13.9 1.0
O B:LYS70 4.1 14.1 1.0
CB B:THR293 4.3 14.5 1.0
O B:HOH776 4.5 14.8 1.0
C B:GLN73 4.6 18.9 1.0
C B:GLY74 4.7 14.1 1.0
CB B:SER71 4.7 13.5 1.0
N B:GLY72 4.8 14.2 1.0
N B:GLN73 4.9 15.4 1.0
N B:SER71 4.9 13.1 1.0
N B:TYR75 4.9 12.3 1.0
CA B:ALA396 4.9 11.7 1.0
N B:THR292 4.9 13.3 1.0
C B:LYS70 4.9 14.8 1.0
CD1 B:TYR75 4.9 13.9 1.0
CG2 B:THR293 5.0 13.8 1.0
C B:GLY72 5.0 17.8 1.0

Reference:

J.D.Scott, S.W.Li, A.P.Brunskill, X.Chen, K.Cox, J.N.Cumming, M.Forman, E.J.Gilbert, R.A.Hodgson, L.A.Hyde, Q.Jiang, U.Iserloh, I.Kazakevich, R.Kuvelkar, H.Mei, J.Meredith, J.Misiaszek, P.Orth, L.M.Rossiter, M.Slater, J.Stone, C.O.Strickland, J.H.Voigt, G.Wang, H.Wang, Y.Wu, W.J.Greenlee, E.M.Parker, M.E.Kennedy, A.W.Stamford. Discovery of the 3-Imino-1,2,4-Thiadiazinane 1,1-Dioxide Derivative Verubecestat (Mk-8931)-A Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor For the Treatment of Alzheimer'S Disease. J. Med. Chem. V. 59 10435 2016.
ISSN: ISSN 1520-4804
PubMed: 27933948
DOI: 10.1021/ACS.JMEDCHEM.6B00307
Page generated: Tue Jul 15 04:00:04 2025

Last articles

Mn in 9LJU
Mn in 9LJW
Mn in 9LJS
Mn in 9LJR
Mn in 9LJT
Mn in 9LJV
Mg in 9UA2
Mg in 9R96
Mg in 9VM1
Mg in 9P01
© Copyright 2008-2020 by atomistry.com
Home   |    Site Map   |    Copyright   |    Contact us   |    Privacy