Zinc in PDB 4tpp: 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors

All present enzymatic activity of 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors:
3.1.4.17; 3.1.4.35;

The structure of 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors, PDB code: 4tpp was solved by S.Chmait, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	48.73 / 2.65
Space group	F 2 3
Cell size a, b, c (Å), α, β, γ (°)	253.216, 253.216, 253.216, 90.00, 90.00, 90.00
R / Rfree (%)	16.7 / 19.8

The binding sites of Zinc atom in the 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors (pdb code 4tpp). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 4 binding sites of Zinc where determined in the 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors, PDB code: 4tpp:
Jump to Zinc binding site number: 1; 2; 3; 4;

Zinc binding site 1 out of 4 in the 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn1001 b:49.3 occ:1.00 OD2 A:ASP554 2.0 49.9 1.0 OD1 A:ASP664 2.0 54.6 1.0 NE2 A:HIS553 2.2 38.8 1.0 NE2 A:HIS519 2.3 39.0 1.0 CG A:ASP664 2.9 43.7 1.0 CD2 A:HIS553 3.1 46.4 1.0 CG A:ASP554 3.1 46.0 1.0 OD2 A:ASP664 3.1 53.2 1.0 O A:HOH1133 3.1 37.1 1.0 ZN A:ZN1002 3.2 53.5 1.0 CD2 A:HIS519 3.2 45.0 1.0 CE1 A:HIS553 3.2 50.0 1.0 CE1 A:HIS519 3.3 41.6 1.0 CD2 A:HIS515 3.5 52.2 1.0 OD1 A:ASP554 3.6 45.7 1.0 NE2 A:HIS515 3.8 48.5 1.0 CG A:HIS553 4.2 36.0 1.0 ND1 A:HIS553 4.3 30.0 1.0 CB A:ASP664 4.3 40.2 1.0 CB A:ASP554 4.3 39.4 1.0 CG A:HIS519 4.4 44.3 1.0 ND1 A:HIS519 4.4 45.8 1.0 O A:HOH1144 4.4 40.2 1.0 CG A:HIS515 4.8 47.4 1.0 CA A:ASP664 4.8 46.3 1.0 O A:ASP664 4.9 56.2 1.0

Zinc binding site 2 out of 4 in the 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn1002 b:53.5 occ:1.00 OD1 A:ASP554 2.0 45.7 1.0 O A:HOH1144 2.1 40.2 1.0 O A:HOH1147 2.2 49.5 1.0 O A:HOH1145 2.5 53.1 1.0 CG A:ASP554 2.8 46.0 1.0 OD2 A:ASP554 3.0 49.9 1.0 ZN A:ZN1001 3.2 49.3 1.0 O A:HOH1133 3.2 37.1 1.0 O A:HOH1132 3.3 60.8 1.0 O A:HOH1143 3.8 63.7 1.0 CD2 A:HIS553 4.0 46.4 1.0 OD2 A:ASP664 4.1 53.2 1.0 NE2 A:HIS515 4.1 48.5 1.0 CD2 A:HIS515 4.1 52.2 1.0 NE2 A:HIS553 4.2 38.8 1.0 CB A:ASP554 4.3 39.4 1.0 O A:THR623 4.4 57.0 1.0 CD2 A:HIS557 4.4 44.7 1.0 O A:HIS553 4.4 50.7 1.0 NE2 A:HIS585 4.5 48.5 1.0 OG1 A:THR623 4.5 54.6 1.0 NE2 A:HIS557 4.5 44.0 1.0 CB A:THR623 4.6 38.9 1.0 OE2 A:GLU582 4.6 50.2 1.0 OD1 A:ASP664 4.6 54.6 1.0 CD2 A:HIS585 4.8 45.9 1.0 CG A:ASP664 4.8 43.7 1.0 CA A:ASP554 4.8 49.1 1.0

Zinc binding site 3 out of 4 in the 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn801 b:48.3 occ:1.00 OD1 B:ASP664 1.9 44.6 1.0 OD2 B:ASP554 2.0 49.6 1.0 NE2 B:HIS553 2.1 40.3 1.0 NE2 B:HIS519 2.4 46.5 1.0 CG B:ASP664 2.8 45.7 1.0 CD2 B:HIS553 2.9 45.4 1.0 OD2 B:ASP664 3.0 52.9 1.0 CG B:ASP554 3.0 48.8 1.0 CE1 B:HIS553 3.1 48.0 1.0 ZN B:ZN802 3.2 54.1 1.0 CE1 B:HIS519 3.3 41.2 1.0 CD2 B:HIS519 3.4 47.6 1.0 O B:HOH922 3.5 33.7 1.0 OD1 B:ASP554 3.6 50.5 1.0 O B:HOH923 3.9 50.7 1.0 NE2 B:HIS515 4.1 60.2 1.0 CG B:HIS553 4.1 34.2 1.0 CB B:ASP664 4.2 37.1 1.0 O B:HOH920 4.2 62.8 1.0 ND1 B:HIS553 4.2 30.3 1.0 O B:HOH937 4.2 70.8 1.0 CB B:ASP554 4.2 43.6 1.0 CD2 B:HIS515 4.4 61.5 1.0 ND1 B:HIS519 4.5 44.3 1.0 CG B:HIS519 4.5 40.6 1.0 CE1 B:HIS515 4.6 60.2 1.0 CA B:ASP664 4.7 44.8 1.0 O B:ASP664 4.8 47.9 1.0 CG B:HIS515 5.0 44.9 1.0

Zinc binding site 4 out of 4 in the 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 4 of 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn802 b:54.1 occ:1.00 O B:HOH923 1.8 50.7 1.0 OD1 B:ASP554 2.0 50.5 1.0 O B:HOH936 2.0 40.0 1.0 O B:HOH937 2.3 70.8 1.0 O B:HOH922 2.6 33.7 1.0 CG B:ASP554 2.8 48.8 1.0 OD2 B:ASP554 2.9 49.6 1.0 ZN B:ZN801 3.2 48.3 1.0 OE2 B:GLU582 3.8 57.5 1.0 CE1 B:HIS515 3.9 60.2 1.0 CD2 B:HIS553 4.0 45.4 1.0 OD2 B:ASP664 4.1 52.9 1.0 CD2 B:HIS557 4.1 48.1 1.0 NE2 B:HIS557 4.2 41.6 1.0 NE2 B:HIS553 4.2 40.3 1.0 CB B:ASP554 4.2 43.6 1.0 O B:THR623 4.4 55.3 1.0 OG1 B:THR623 4.4 56.5 1.0 NE2 B:HIS515 4.4 60.2 1.0 O B:HOH921 4.4 51.8 1.0 NE2 B:HIS585 4.4 48.1 1.0 O B:HIS553 4.4 51.7 1.0 ND1 B:HIS515 4.4 64.3 1.0 CB B:THR623 4.6 45.8 1.0 O B:HOH919 4.6 60.4 1.0 OD1 B:ASP664 4.6 44.6 1.0 CD2 B:HIS585 4.7 48.7 1.0 CG B:ASP664 4.8 45.7 1.0 CA B:ASP554 4.8 44.7 1.0 CD B:GLU582 4.9 48.3 1.0

R.M.Rzasa, M.J.Frohn, K.L.Andrews, S.Chmait, N.Chen, J.G.Clarine, C.Davis, H.A.Eastwood, D.B.Horne, E.Hu, A.D.Jones, M.R.Kaller, R.K.Kunz, S.Miller, H.Monenschein, T.Nguyen, A.J.Pickrell, A.Porter, A.Reichelt, X.Zhao, J.J.Treanor, J.R.Allen. Synthesis and Preliminary Biological Evaluation of Potent and Selective 2-(3-Alkoxy-1-Azetidinyl) Quinolines As Novel PDE10A Inhibitors with Improved Solubility. Bioorg.Med.Chem. V. 22 6570 2014.
ISSN: ESSN 1464-3391
PubMed: 25456383
DOI: 10.1016/J.BMC.2014.10.013