Zinc in PDB 4xry: Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex

All present enzymatic activity of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex:
1.14.14.1;

The structure of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex, PDB code: 4xry 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)	39.16 / 2.50
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	57.064, 192.341, 247.304, 90.00, 90.00, 90.00
R / Rfree (%)	20.8 / 25.1

The structure of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex also contains other interesting chemical elements:

Fluorine	(F)	8 atoms
Iron	(Fe)	4 atoms

Pages:

>>> Page 1 <<< Page 2, Binding sites: 11 - 17;

Binding sites:

The binding sites of Zinc atom in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex (pdb code 4xry). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 17 binding sites of Zinc where determined in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex, PDB code: 4xry:
Jump to Zinc binding site number: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10;

Zinc binding site 1 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn603 b:33.5 occ:1.00 OE2 A:GLU273 1.9 28.5 1.0 OD2 A:ASP270 2.0 38.5 1.0 NE2 A:HIS258 2.1 24.8 1.0 CD A:GLU273 2.8 34.5 1.0 CG A:ASP270 2.9 31.6 1.0 CE1 A:HIS258 3.0 33.3 1.0 CD2 A:HIS258 3.1 28.2 1.0 OD1 A:ASP270 3.2 25.6 1.0 CG A:GLU273 3.3 27.9 1.0 O A:CYS191 3.6 40.1 1.0 OE1 A:GLU273 3.9 29.3 1.0 O A:HOH704 4.2 37.7 1.0 ND1 A:HIS258 4.2 42.8 1.0 C A:CYS191 4.2 33.7 1.0 CG A:HIS258 4.2 26.3 1.0 CB A:ASP270 4.3 24.5 1.0 NH2 A:ARG269 4.4 37.4 1.0 NE A:ARG269 4.6 51.3 1.0 CB A:GLU273 4.6 29.5 1.0 CA A:GLY192 4.7 35.2 1.0 CB A:ARG269 4.7 40.9 1.0 N A:GLY192 4.7 41.3 1.0 N A:ASP270 4.9 33.5 1.0 CA A:CYS191 4.9 33.3 1.0 CZ A:ARG269 5.0 38.2 1.0

Zinc binding site 2 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn604 b:69.7 occ:1.00 SG A:CYS191 2.4 64.2 1.0 CB A:CYS191 2.9 50.5 1.0 CA A:CYS191 4.2 33.3 1.0 OG1 A:THR190 4.2 54.1 1.0 N A:CYS191 4.3 36.3 1.0 CB A:LEU254 4.7 29.6 1.0 CB A:ALA187 4.7 34.4 1.0 O A:ALA187 4.7 35.0 1.0 CZ A:PHE195 4.7 34.1 1.0 CA A:ALA187 4.8 37.6 1.0 CE1 A:PHE195 4.9 30.4 1.0 CB A:THR190 5.0 39.0 1.0

Zinc binding site 3 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn605 b:75.1 occ:1.00 ND1 A:HIS463 1.9 64.2 1.0 O A:HOH736 2.1 45.2 1.0 O A:HOH734 2.2 65.7 1.0 CE1 A:HIS463 2.9 67.2 1.0 CG A:HIS463 2.9 57.6 1.0 CB A:HIS463 3.3 43.4 1.0 CA A:HIS463 3.8 52.9 1.0 NE2 A:HIS463 4.0 70.7 1.0 CD2 A:HIS463 4.0 61.1 1.0 O A:HIS463 4.2 59.2 1.0 C A:HIS463 4.5 54.3 1.0 C A:ARG497 4.7 74.3 1.0 O A:GLN341 4.8 82.4 1.0 N A:ARG497 4.9 72.1 1.0 O A:HOH708 5.0 51.4 1.0

Zinc binding site 4 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 4 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn606 b:46.5 occ:1.00 OD2 A:ASP422 2.0 43.3 1.0 OD2 B:ASP422 2.0 43.4 1.0 ND1 A:HIS426 2.0 55.1 1.0 ND1 B:HIS426 2.0 50.1 1.0 CE1 A:HIS426 2.9 61.0 1.0 CG B:ASP422 3.0 38.7 1.0 CG B:HIS426 3.0 53.1 1.0 CE1 B:HIS426 3.0 55.2 1.0 CG A:HIS426 3.0 59.9 1.0 CG A:ASP422 3.1 40.7 1.0 CB B:HIS426 3.3 42.0 1.0 OD1 B:ASP422 3.4 40.5 1.0 CB A:HIS426 3.4 39.0 1.0 OD1 A:ASP422 3.5 42.9 1.0 CB B:GLN424 4.0 52.3 1.0 CB A:GLN424 4.0 55.8 1.0 NE2 A:HIS426 4.0 68.7 1.0 NE2 B:HIS426 4.1 63.4 1.0 CD2 B:HIS426 4.1 46.2 1.0 CD2 A:HIS426 4.1 49.5 1.0 CB B:ASP422 4.2 36.3 1.0 CB A:ASP422 4.3 40.1 1.0 CA B:HIS426 4.6 46.0 1.0 CG A:GLN424 4.6 63.4 1.0 N B:HIS426 4.6 40.8 1.0 CG B:GLN424 4.6 58.4 1.0 CA A:HIS426 4.7 48.6 1.0 N A:HIS426 4.8 44.3 1.0

Zinc binding site 5 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 5 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn603 b:36.4 occ:1.00 OE2 B:GLU273 1.9 29.3 1.0 NE2 B:HIS258 2.0 30.0 1.0 OD2 B:ASP270 2.0 44.7 1.0 CD B:GLU273 2.8 36.6 1.0 CE1 B:HIS258 2.9 33.3 1.0 CG B:ASP270 2.9 33.2 1.0 CD2 B:HIS258 3.1 36.1 1.0 OD1 B:ASP270 3.1 31.7 1.0 CG B:GLU273 3.3 33.6 1.0 O B:CYS191 3.5 43.7 1.0 OE1 B:GLU273 3.9 38.5 1.0 O B:HOH701 3.9 32.7 1.0 ND1 B:HIS258 4.1 39.7 1.0 CG B:HIS258 4.2 26.5 1.0 C B:CYS191 4.2 37.3 1.0 O B:HOH708 4.3 46.2 1.0 CB B:ASP270 4.3 26.3 1.0 NH2 B:ARG269 4.4 35.7 1.0 NE B:ARG269 4.5 55.0 1.0 CA B:GLY192 4.6 37.7 1.0 CB B:GLU273 4.6 34.3 1.0 CB B:ARG269 4.6 39.2 1.0 N B:GLY192 4.7 38.0 1.0 CZ B:ARG269 4.9 44.4 1.0 N B:ASP270 4.9 37.9 1.0

Zinc binding site 6 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 6 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn604 b:70.3 occ:1.00 SG B:CYS191 2.4 71.3 1.0 CB B:CYS191 2.9 45.9 1.0 OG1 B:THR190 4.3 48.7 1.0 CA B:CYS191 4.3 38.3 1.0 CB B:LEU254 4.4 26.8 1.0 CE1 B:PHE303 4.5 64.8 1.0 N B:CYS191 4.5 37.1 1.0 CD1 B:LEU254 4.6 39.1 1.0 CB B:ALA187 4.8 26.5 1.0 CZ B:PHE195 4.8 34.4 1.0 CA B:ALA187 4.8 35.4 1.0 O B:ALA187 4.8 31.6 1.0 CD1 B:PHE303 4.9 58.4 1.0 CE1 B:PHE195 4.9 31.1 1.0

Zinc binding site 7 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 7 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn605 b:76.9 occ:1.00 ND1 B:HIS463 2.0 54.0 1.0 O B:HOH730 2.1 55.3 1.0 CG B:HIS463 2.9 53.6 1.0 CE1 B:HIS463 3.0 64.0 1.0 CB B:HIS463 3.2 41.9 1.0 CA B:HIS463 3.7 51.4 1.0 O B:HIS463 4.0 51.6 1.0 CD2 B:HIS463 4.0 58.9 1.0 NE2 B:HIS463 4.1 61.1 1.0 OE1 B:GLN341 4.2 81.5 1.0 O B:ARG497 4.3 75.6 1.0 C B:HIS463 4.3 49.8 1.0 N B:ARG497 4.8 66.6 1.0 O B:GLN341 4.8 85.1 1.0 O B:HOH734 4.9 53.5 1.0 N B:HIS463 5.0 52.1 1.0

Zinc binding site 8 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 8 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn603 b:37.2 occ:1.00 OE2 C:GLU273 2.0 27.0 1.0 NE2 C:HIS258 2.0 30.4 1.0 OD2 C:ASP270 2.1 42.3 1.0 CD C:GLU273 2.9 31.4 1.0 CE1 C:HIS258 2.9 31.8 1.0 CG C:ASP270 3.0 35.9 1.0 CD2 C:HIS258 3.0 41.3 1.0 OD1 C:ASP270 3.2 30.4 1.0 CG C:GLU273 3.3 29.8 1.0 O C:CYS191 3.8 30.4 1.0 OE1 C:GLU273 3.9 26.7 1.0 O C:HOH707 4.0 39.1 1.0 ND1 C:HIS258 4.1 31.0 1.0 CG C:HIS258 4.1 24.2 1.0 C C:CYS191 4.3 35.2 1.0 CB C:ASP270 4.4 34.4 1.0 CA C:GLY192 4.6 40.8 1.0 CB C:GLU273 4.6 33.2 1.0 NE C:ARG269 4.6 52.6 1.0 CB C:ARG269 4.7 45.8 1.0 NH2 C:ARG269 4.7 29.8 1.0 N C:GLY192 4.8 39.2 1.0

Zinc binding site 9 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 9 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn604 b:69.9 occ:1.00 SG C:CYS191 2.2 75.1 1.0 CB C:CYS191 3.1 50.4 1.0 CD1 C:LEU254 4.5 31.0 1.0 CB C:LEU254 4.5 32.1 1.0 CA C:CYS191 4.5 36.9 1.0 OG1 C:THR190 4.6 44.5 1.0 CZ C:PHE195 4.8 32.7 1.0 CD1 C:LEU251 4.8 39.6 1.0 CE1 C:PHE195 4.8 23.4 1.0 O C:ALA187 4.9 32.0 1.0 N C:CYS191 4.9 38.7 1.0 CB C:ALA187 4.9 29.6 1.0 CA C:ALA187 5.0 36.4 1.0

Zinc binding site 10 out of 17 in the Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 10 of Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn605 b:89.4 occ:1.00 NE2 C:HIS324 2.1 65.2 1.0 O C:HOH734 2.2 34.1 1.0 CE1 C:HIS324 2.5 59.1 1.0 CD2 C:HIS324 3.3 55.6 1.0 ND1 C:HIS324 3.8 67.6 1.0 CG C:HIS324 4.2 52.6 1.0 CB C:PHE415 4.4 48.0 1.0 N C:PHE415 4.7 43.0 1.0 CG C:HIS477 4.8 60.0 1.0 ND1 C:HIS477 4.8 81.7 1.0 CD2 C:HIS477 4.9 79.2 1.0 CE1 C:HIS477 5.0 95.7 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