Sodium in PDB 4xrz: Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex

All present enzymatic activity of Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex:
1.14.14.1;

The structure of Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex, PDB code: 4xrz was solved by E.F.Johnson, Y.Fan, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	38.93 / 2.40
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	57.543, 192.480, 244.883, 90.00, 90.00, 90.00
R / Rfree (%)	21.7 / 25.4

The structure of Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex also contains other interesting chemical elements:

Fluorine	(F)	8 atoms
Zinc	(Zn)	12 atoms
Iron	(Fe)	4 atoms

The binding sites of Sodium atom in the Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex (pdb code 4xrz). This binding sites where shown within 5.0 Angstroms radius around Sodium atom.
In total 4 binding sites of Sodium where determined in the Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex, PDB code: 4xrz:
Jump to Sodium binding site number: 1; 2; 3; 4;

Sodium binding site 1 out of 4 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex


Mono view


Stereo pair view

A full contact list of Sodium with other atoms in the Na binding site number 1 of Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex within 5.0Å range: probe atom residue distance (Å) B Occ A:Na608 b:50.9 occ:1.00 O A:HOH752 2.4 49.9 1.0 O A:HOH764 2.5 49.6 1.0 O A:HOH720 2.8 24.4 1.0 OE2 A:GLU446 3.2 36.8 1.0 O A:HOH788 3.3 58.9 1.0 OE1 A:GLU446 3.3 38.9 1.0 CD A:GLU446 3.6 46.2 1.0 O A:SER437 4.3 25.2 1.0 O A:HOH747 4.3 32.0 1.0 CB A:PHE436 4.4 16.6 1.0 CD1 A:PHE436 4.4 26.5 1.0 O A:HOH762 4.5 40.8 1.0 O A:PHE433 4.8 30.3 1.0 CG A:PHE436 4.9 25.4 1.0 CD2 A:LEU434 4.9 19.7 1.0

Sodium binding site 2 out of 4 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex


Mono view


Stereo pair view

A full contact list of Sodium with other atoms in the Na binding site number 2 of Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex within 5.0Å range: probe atom residue distance (Å) B Occ B:Na606 b:42.1 occ:1.00 OD2 B:ASP301 2.4 36.5 1.0 N B:VAL119 2.6 29.1 1.0 N B:PHE120 3.1 30.9 1.0 CG B:ASP301 3.1 38.7 1.0 CB B:ASP301 3.2 32.0 1.0 O B:HOH721 3.3 35.2 1.0 CA B:VAL119 3.4 27.6 1.0 CB B:VAL119 3.6 31.6 1.0 C B:GLY118 3.6 39.1 1.0 CA B:GLY118 3.7 33.5 1.0 C B:VAL119 3.8 26.6 1.0 CB B:PHE120 4.0 35.7 1.0 CD1 B:PHE120 4.1 46.4 1.0 CA B:PHE120 4.1 31.4 1.0 CG2 B:VAL119 4.2 25.8 1.0 O B:ILE297 4.3 33.1 1.0 OD1 B:ASP301 4.3 36.7 1.0 CA B:VAL298 4.5 30.8 1.0 CG B:PHE120 4.5 36.3 1.0 O B:GLN117 4.6 38.8 1.0 CG2 B:ILE297 4.6 28.8 1.0 CA B:ASP301 4.7 35.9 1.0 O B:GLY118 4.8 34.1 1.0 C B:ILE297 4.8 32.7 1.0 CG1 B:VAL119 4.8 29.3 1.0 N B:GLY118 4.9 32.2 1.0 N B:VAL298 4.9 30.3 1.0 O B:VAL298 5.0 31.2 1.0 O B:VAL119 5.0 39.3 1.0

Sodium binding site 3 out of 4 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex


Mono view


Stereo pair view

A full contact list of Sodium with other atoms in the Na binding site number 3 of Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex within 5.0Å range: probe atom residue distance (Å) B Occ C:Na607 b:50.6 occ:1.00 OD2 C:ASP301 2.3 46.6 1.0 N C:VAL119 2.7 30.2 1.0 N C:PHE120 3.0 38.5 1.0 CG C:ASP301 3.0 42.1 1.0 CB C:ASP301 3.1 31.4 1.0 CB C:VAL119 3.3 37.0 1.0 CA C:VAL119 3.3 39.8 1.0 C C:VAL119 3.7 32.7 1.0 O C:HOH724 3.7 33.3 1.0 C C:GLY118 3.7 35.0 1.0 CG2 C:VAL119 3.9 28.2 1.0 CB C:PHE120 3.9 42.4 1.0 CA C:GLY118 3.9 40.5 1.0 CA C:PHE120 4.0 33.8 1.0 OD1 C:ASP301 4.2 40.2 1.0 CD1 C:PHE120 4.4 45.1 1.0 O C:ILE297 4.5 32.3 1.0 CG1 C:VAL119 4.5 27.6 1.0 CA C:VAL298 4.6 31.6 1.0 CA C:ASP301 4.6 33.7 1.0 CG C:PHE120 4.7 31.6 1.0 CMD C:HEM601 4.8 25.9 1.0 O C:GLY118 4.9 37.8 1.0 O C:VAL119 4.9 37.4 1.0 O C:VAL298 4.9 34.4 1.0 CG2 C:ILE297 5.0 34.6 1.0

Sodium binding site 4 out of 4 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex


Mono view


Stereo pair view

A full contact list of Sodium with other atoms in the Na binding site number 4 of Human Cytochrome P450 2D6 BACE1 Inhibitor 6 Complex within 5.0Å range: probe atom residue distance (Å) B Occ D:Na607 b:42.5 occ:1.00 OG D:SER135 2.2 34.7 1.0 O D:GLN131 2.5 32.6 1.0 O D:HOH748 3.0 42.9 1.0 OE1 D:GLN131 3.1 28.8 1.0 CB D:SER135 3.3 26.7 1.0 C D:GLN131 3.4 30.2 1.0 CG1 D:VAL298 3.5 21.1 1.0 CD1 D:PHE134 3.5 34.9 1.0 N D:SER135 3.7 28.6 1.0 CA D:GLN131 3.8 31.4 1.0 CB D:GLN131 3.9 25.9 1.0 CA D:SER135 3.9 29.0 1.0 CG2 D:VAL119 3.9 30.4 1.0 CD D:GLN131 4.1 32.1 1.0 CG2 D:VAL298 4.2 26.9 1.0 CE1 D:PHE134 4.3 28.6 1.0 CB D:PHE134 4.4 28.1 1.0 CG D:PHE134 4.4 30.6 1.0 N D:ARG132 4.5 30.7 1.0 CB D:VAL298 4.5 30.1 1.0 CG D:GLN131 4.5 28.1 1.0 C D:PHE134 4.6 29.2 1.0 CA D:ARG132 4.9 32.0 1.0 CA D:PHE134 5.0 34.8 1.0

M.A.Brodney, E.M.Beck, C.R.Butler, G.Barreiro, E.F.Johnson, D.Riddell, K.Parris, C.E.Nolan, Y.Fan, K.Atchison, C.Gonzales, A.E.Robshaw, S.D.Doran, M.W.Bundesmann, L.Buzon, J.Dutra, K.Henegar, E.Lachapelle, X.Hou, B.N.Rogers, J.Pandit, R.Lira, L.Martinez-Alsina, P.Mikochik, J.C.Murray, K.Ogilvie, L.Price, S.M.Sakya, A.Yu, Y.Zhang, B.T.O'neill. Utilizing Structures of CYP2D6 and BACE1 Complexes to Reduce Risk of Drug-Drug Interactions with A Novel Series of Centrally Efficacious BACE1 Inhibitors. J.Med.Chem. V. 58 3223 2015.
ISSN: ISSN 0022-2623
PubMed: 25781223
DOI: 10.1021/ACS.JMEDCHEM.5B00191