Atomistry » Fluorine » PDB 5he2-5hti » 5he7
Atomistry »
  Fluorine »
    PDB 5he2-5hti »
      5he7 »

Fluorine in PDB 5he7: Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One

Enzymatic activity of Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One

All present enzymatic activity of Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One:
3.4.23.46;

Protein crystallography data

The structure of Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One, PDB code: 5he7 was solved by P.Orth, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 19.88 / 1.71
Space group P 21 21 21
Cell size a, b, c (Å), α, β, γ (°) 86.530, 89.270, 131.360, 90.00, 90.00, 90.00
R / Rfree (%) 19 / 21.6

Fluorine Binding Sites:

The binding sites of Fluorine atom in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One (pdb code 5he7). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One, PDB code: 5he7:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in 5he7

Go back to Fluorine Binding Sites List in 5he7
Fluorine binding site 1 out of 6 in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One


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 (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F501

b:25.0
occ:1.00
 F2 A:60X501 0.0 25.0 1.0
C17 A:60X501 1.4 21.7 1.0
C16 A:60X501 2.3 19.4 1.0
C12 A:60X501 2.4 16.9 1.0
OH A:TYR132 2.8 66.8 1.0
C6 A:60X501 2.9 16.7 1.0
C5 A:60X501 3.0 16.5 1.0
CZ A:TYR132 3.0 64.2 1.0
C10 A:60X501 3.0 15.8 1.0
CE2 A:TYR132 3.4 56.8 1.0
CE1 A:PHE169 3.4 26.4 1.0
CD1 A:PHE169 3.5 26.3 1.0
C15 A:60X501 3.6 22.7 1.0
C13 A:60X501 3.6 17.1 1.0
CE1 A:TYR132 3.6 58.5 1.0
N2 A:60X501 3.8 17.1 1.0
C11 A:60X501 4.0 17.3 1.0
CD1 A:ILE179 4.0 20.5 1.0
C14 A:60X501 4.1 19.2 1.0
C9 A:60X501 4.2 20.8 1.0
CD2 A:TYR132 4.3 56.0 1.0
N3 A:60X501 4.3 14.1 1.0
CD1 A:TYR132 4.5 57.5 1.0
CZ A:PHE169 4.6 24.4 1.0
CG A:PHE169 4.6 23.2 1.0
F1 A:60X501 4.7 29.6 1.0
O1 A:60X501 4.7 24.1 1.0
O A:HOH967 4.7 51.6 1.0
O A:HOH636 4.7 33.9 1.0
CG A:TYR132 4.8 55.5 1.0
C2 A:60X501 4.8 19.8 1.0
N1 A:60X501 5.0 20.4 1.0

Fluorine binding site 2 out of 6 in 5he7

Go back to Fluorine Binding Sites List in 5he7
Fluorine binding site 2 out of 6 in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One


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 (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F501

b:29.6
occ:1.00
 F1 A:60X501 0.0 29.6 1.0
C15 A:60X501 1.4 22.7 1.0
C16 A:60X501 2.3 19.4 1.0
C14 A:60X501 2.3 19.2 1.0
CZ2 A:TRP176 3.1 23.8 1.0
CD1 A:ILE171 3.3 37.9 1.0
CH2 A:TRP176 3.4 23.9 1.0
C17 A:60X501 3.6 21.7 1.0
C13 A:60X501 3.6 17.1 1.0
O A:HOH636 3.7 33.9 1.0
O A:HOH951 3.7 48.3 1.0
CG1 A:ILE171 4.1 34.8 1.0
C12 A:60X501 4.1 16.9 1.0
CE2 A:TRP176 4.3 24.5 1.0
O A:PHE169 4.3 29.8 1.0
CD1 A:LEU91 4.5 24.5 1.0
O A:HOH912 4.5 35.6 1.0
F2 A:60X501 4.7 25.0 1.0
CZ3 A:TRP176 4.8 23.1 1.0
O A:HOH645 4.8 34.2 1.0
NE1 A:TRP176 4.9 22.2 1.0
O A:GLN73 4.9 20.7 1.0
CD1 A:ILE179 5.0 20.5 1.0

Fluorine binding site 3 out of 6 in 5he7

Go back to Fluorine Binding Sites List in 5he7
Fluorine binding site 3 out of 6 in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One


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 (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F501

b:27.3
occ:1.00
 F A:60X501 0.0 27.3 1.0
C A:60X501 1.3 24.6 1.0
C3 A:60X501 2.4 25.7 1.0
C1 A:60X501 2.4 23.2 1.0
O A:60X501 2.7 28.1 1.0
C18 A:60X501 3.0 21.8 1.0
OD1 A:ASN98 3.1 16.0 1.0
O A:HOH795 3.1 17.9 1.0
CG A:ASN98 3.4 21.0 1.0
N1 A:60X501 3.6 20.4 1.0
CG A:ARG189 3.6 25.1 1.0
CB A:ASN98 3.6 12.1 1.0
N A:60X501 3.6 20.4 1.0
CZ2 A:TRP137 3.9 27.8 1.0
CG1 A:VAL130 4.0 36.9 1.0
C2 A:60X501 4.0 19.8 1.0
CG2 A:VAL130 4.0 36.9 1.0
C4 A:60X501 4.1 29.6 1.0
CB A:ARG189 4.1 19.4 1.0
ND2 A:ASN98 4.4 14.0 1.0
CE2 A:TRP137 4.6 29.2 1.0
CB A:VAL130 4.6 36.9 1.0
NE1 A:TRP137 4.6 28.8 1.0
N A:ASN98 4.6 11.8 1.0
N A:ARG189 4.7 18.4 1.0
CA A:ASN98 4.8 12.2 1.0
CH2 A:TRP137 4.8 26.4 1.0
CB A:SER96 4.8 14.2 1.0
CD A:ARG189 5.0 32.9 1.0

Fluorine binding site 4 out of 6 in 5he7

Go back to Fluorine Binding Sites List in 5he7
Fluorine binding site 4 out of 6 in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One


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 (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F501

b:19.6
occ:1.00
 F2 B:60X501 0.0 19.6 1.0
C17 B:60X501 1.4 17.3 1.0
C16 B:60X501 2.3 17.4 1.0
C12 B:60X501 2.4 13.6 1.0
OH B:TYR132 2.9 25.7 1.0
C6 B:60X501 2.9 13.4 1.0
C5 B:60X501 3.0 13.6 1.0
C10 B:60X501 3.0 13.2 1.0
CZ B:TYR132 3.2 27.8 1.0
CD1 B:PHE169 3.3 18.4 1.0
O B:HOH845 3.4 34.8 1.0
C15 B:60X501 3.6 19.4 1.0
CE1 B:PHE169 3.6 18.2 1.0
C13 B:60X501 3.6 14.1 1.0
CE2 B:TYR132 3.6 22.8 1.0
N2 B:60X501 3.8 13.7 1.0
CE1 B:TYR132 3.9 22.4 1.0
CD1 B:ILE179 4.0 16.3 1.0
C11 B:60X501 4.0 15.8 1.0
C14 B:60X501 4.1 15.5 1.0
C9 B:60X501 4.2 18.2 1.0
CG B:PHE169 4.3 15.4 1.0
N3 B:60X501 4.3 13.2 1.0
O B:HOH950 4.5 48.4 1.0
CA B:PHE169 4.6 14.8 1.0
CD2 B:TYR132 4.6 22.1 1.0
O1 B:60X501 4.7 23.5 1.0
F1 B:60X501 4.7 22.5 1.0
O B:PHE169 4.7 18.7 1.0
CZ B:PHE169 4.7 16.9 1.0
CD1 B:TYR132 4.8 23.2 1.0
O B:HOH855 4.8 22.7 1.0
CB B:PHE169 4.8 15.2 1.0
C2 B:60X501 4.8 15.7 1.0

Fluorine binding site 5 out of 6 in 5he7

Go back to Fluorine Binding Sites List in 5he7
Fluorine binding site 5 out of 6 in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F501

b:22.5
occ:1.00
 F1 B:60X501 0.0 22.5 1.0
C15 B:60X501 1.4 19.4 1.0
C16 B:60X501 2.3 17.4 1.0
C14 B:60X501 2.3 15.5 1.0
CZ2 B:TRP176 3.1 16.9 1.0
O B:HOH855 3.3 22.7 1.0
CD1 B:ILE171 3.3 26.1 1.0
O B:HOH1055 3.4 50.7 1.0
CH2 B:TRP176 3.5 17.4 1.0
C17 B:60X501 3.6 17.3 1.0
O B:HOH968 3.6 40.2 1.0
C13 B:60X501 3.6 14.1 1.0
O B:PHE169 3.8 18.7 1.0
CG1 B:ILE171 3.9 23.1 1.0
C12 B:60X501 4.1 13.6 1.0
CD1 B:LEU91 4.2 21.3 1.0
O B:HOH944 4.3 32.4 1.0
CE2 B:TRP176 4.4 17.5 1.0
F2 B:60X501 4.7 19.6 1.0
O B:HOH845 4.8 34.8 1.0
CZ3 B:TRP176 4.8 16.3 1.0
CD1 B:ILE179 4.8 16.3 1.0
O B:GLN73 4.8 21.2 1.0
O B:HOH699 5.0 29.7 1.0

Fluorine binding site 6 out of 6 in 5he7

Go back to Fluorine Binding Sites List in 5he7
Fluorine binding site 6 out of 6 in the Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Bace-1 in Complex with (4AR,7AS)-7A-(2,4-Difluorophenyl)-6-(5-Fluoro- 4-Methoxy-6-Methylpyrimidin-2-Yl)-2-Imino-3-Methyloctahydro-4H- Pyrrolo[3,4-D]Pyrimidin-4-One within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F501

b:19.9
occ:1.00
 F B:60X501 0.0 19.9 1.0
C B:60X501 1.3 17.2 1.0
C3 B:60X501 2.4 16.8 1.0
C1 B:60X501 2.4 14.8 1.0
O B:60X501 2.7 16.5 1.0
C18 B:60X501 2.9 17.0 1.0
O B:HOH809 3.0 16.1 1.0
OD1 B:ASN98 3.1 12.1 1.0
CG B:ASN98 3.4 17.8 1.0
CZ2 B:TRP137 3.5 16.9 1.0
CB B:ASN98 3.6 11.9 1.0
N1 B:60X501 3.6 15.5 1.0
N B:60X501 3.6 14.9 1.0
CG B:ARG189 3.7 17.0 1.0
C2 B:60X501 4.0 15.7 1.0
CG1 B:VAL130 4.1 17.2 1.0
NE1 B:TRP137 4.1 16.5 1.0
C4 B:60X501 4.1 16.4 1.0
CE2 B:TRP137 4.2 16.9 1.0
CB B:ARG189 4.2 14.3 1.0
CG2 B:VAL130 4.2 18.7 1.0
ND2 B:ASN98 4.4 15.3 1.0
N B:ASN98 4.5 10.6 1.0
CH2 B:TRP137 4.6 16.7 1.0
CB B:SER96 4.6 14.2 1.0
CA B:ASN98 4.7 10.9 1.0
CB B:VAL130 4.7 17.1 1.0
N B:ARG189 4.8 13.9 1.0

Reference:

M.Mandal, Y.Wu, J.Misiaszek, G.Li, A.Buevich, J.P.Caldwell, X.Liu, R.D.Mazzola, P.Orth, C.Strickland, J.Voigt, H.Wang, Z.Zhu, X.Chen, M.Grzelak, L.A.Hyde, R.Kuvelkar, P.T.Leach, G.Terracina, L.Zhang, Q.Zhang, M.S.Michener, B.Smith, K.Cox, D.Grotz, L.Favreau, K.Mitra, I.Kazakevich, B.A.Mckittrick, W.Greenlee, M.E.Kennedy, E.M.Parker, J.N.Cumming, A.W.Stamford. Structure-Based Design of An Iminoheterocyclic Beta-Site Amyloid Precursor Protein Cleaving Enzyme (Bace) Inhibitor That Lowers Central A Beta in Nonhuman Primates. J.Med.Chem. V. 59 3231 2016.
ISSN: ISSN 0022-2623
PubMed: 26937601
DOI: 10.1021/ACS.JMEDCHEM.5B01995
Page generated: Thu Aug 1 09:50:14 2024

Last articles

Zn in 9JYW
Zn in 9IR4
Zn in 9IR3
Zn in 9GMX
Zn in 9GMW
Zn in 9JEJ
Zn in 9ERF
Zn in 9ERE
Zn in 9EGV
Zn in 9EGW
© Copyright 2008-2020 by atomistry.com
Home   |    Site Map   |    Copyright   |    Contact us   |    Privacy