Zinc in PDB 8di4: Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia

All present enzymatic activity of Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia:
3.1.4.17; 3.1.4.35;

The structure of Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia, PDB code: 8di4 was solved by R.P.Hayes, Y.Yan, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	78.87 / 2.02
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	49.73, 81.36, 157.749, 90, 90, 90
R / Rfree (%)	25 / 29.5

The structure of Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia also contains other interesting chemical elements:

Magnesium

(Mg)

2 atoms

The binding sites of Zinc atom in the Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia (pdb code 8di4). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 2 binding sites of Zinc where determined in the Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia, PDB code: 8di4:
Jump to Zinc binding site number: 1; 2;

Zinc binding site 1 out of 2 in the Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn901 b:40.4 occ:1.00 O A:HOH1003 1.9 20.4 1.0 NE2 A:HIS553 2.1 38.7 1.0 OD2 A:ASP554 2.1 28.4 1.0 OD1 A:ASP664 2.1 22.1 1.0 NE2 A:HIS519 2.1 30.9 1.0 CG A:ASP554 2.8 28.7 1.0 O A:HOH1026 2.8 49.1 1.0 OD1 A:ASP554 2.9 29.1 1.0 CD2 A:HIS553 3.0 37.6 1.0 CG A:ASP664 3.0 25.5 1.0 CE1 A:HIS519 3.1 31.4 1.0 CE1 A:HIS553 3.2 39.3 1.0 CD2 A:HIS519 3.2 29.8 1.0 OD2 A:ASP664 3.3 26.9 1.0 MG A:MG902 3.6 27.2 1.0 CD2 A:HIS515 4.0 40.0 1.0 O A:HOH1046 4.0 34.4 1.0 CG A:HIS553 4.1 36.9 1.0 ND1 A:HIS553 4.2 38.9 1.0 CB A:ASP554 4.2 32.0 1.0 ND1 A:HIS519 4.3 31.0 1.0 CG A:HIS519 4.3 29.4 1.0 NE2 A:HIS515 4.4 39.7 1.0 CB A:ASP664 4.4 28.1 1.0 O A:HOH1052 4.5 41.3 1.0 O A:HOH1005 4.5 31.8 1.0 CG2 A:VAL523 4.8 33.1 1.0 CA A:ASP664 4.8 28.7 1.0 O A:ASP664 4.9 30.3 1.0

Zinc binding site 2 out of 2 in the Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn801 b:60.1 occ:1.00 NE2 B:HIS553 2.1 40.1 1.0 OD1 B:ASP664 2.1 46.2 1.0 NE2 B:HIS519 2.2 39.1 1.0 OD2 B:ASP554 2.2 39.5 1.0 O B:HOH914 2.2 35.4 1.0 CD2 B:HIS553 3.0 39.0 1.0 CG B:ASP664 3.1 43.5 1.0 CG B:ASP554 3.1 39.6 1.0 CE1 B:HIS553 3.1 40.0 1.0 CD2 B:HIS519 3.1 37.4 1.0 CE1 B:HIS519 3.1 39.6 1.0 OD2 B:ASP664 3.3 44.5 1.0 OD1 B:ASP554 3.5 39.7 1.0 MG B:MG802 3.8 29.8 1.0 CD2 B:HIS515 3.8 38.4 1.0 CG B:HIS553 4.1 38.6 1.0 O B:HOH922 4.1 34.7 1.0 ND1 B:HIS553 4.2 40.1 1.0 CB B:ASP554 4.2 37.0 1.0 NE2 B:HIS515 4.3 39.0 1.0 CG B:HIS519 4.3 36.9 1.0 ND1 B:HIS519 4.3 38.8 1.0 CB B:ASP664 4.4 37.5 1.0 O B:HOH924 4.7 32.2 1.0 CG2 B:VAL523 4.8 34.4 1.0 O B:HOH912 4.8 30.2 1.0 CA B:ASP664 4.8 34.4 1.0 O B:HOH930 4.9 36.9 1.0 O B:ASP664 5.0 34.4 1.0 O B:HOH947 5.0 58.3 1.0

M.E.Layton, J.C.Kern, T.J.Hartingh, W.D.Shipe, I.Raheem, M.Kandebo, R.P.Hayes, S.Huszar, D.Eddins, B.Ma, J.Fuerst, G.K.Wollenberg, J.Li, J.Fritzen, G.B.Mcgaughey, J.M.Uslaner, S.M.Smith, P.J.Coleman, C.D.Cox. Discovery of Mk-8189, A Highly Potent and Selective PDE10A Inhibitor For the Treatment of Schizophrenia. J.Med.Chem. V. 66 1157 2023.
ISSN: ISSN 0022-2623
PubMed: 36624931
DOI: 10.1021/ACS.JMEDCHEM.2C01521