Zinc in PDB 4d08: PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor

All present enzymatic activity of PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor:
3.1.4.17;

The structure of PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor, PDB code: 4d08 was solved by P.Buijnsters, J.I.Andres, M.Deangelis, X.Langlois, F.Rombouts, W.Sanderson, G.Tresadern, A.Trabanco, G.Vanhoof, Y.Vanroosbroeck, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	46.34 / 1.90
Space group	P 1
Cell size a, b, c (Å), α, β, γ (°)	56.040, 74.150, 92.770, 109.04, 91.73, 91.34
R / Rfree (%)	21.289 / 24.714

The structure of PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor also contains other interesting chemical elements:

Magnesium

(Mg)

4 atoms

The binding sites of Zinc atom in the PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor (pdb code 4d08). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 4 binding sites of Zinc where determined in the PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor, PDB code: 4d08:
Jump to Zinc binding site number: 1; 2; 3; 4;

Zinc binding site 1 out of 4 in the PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn1001 b:13.9 occ:1.00 OD2 A:ASP697 2.0 12.0 1.0 O A:HOH2076 2.0 12.9 1.0 O A:HOH2062 2.0 14.5 1.0 OD1 A:ASP808 2.0 13.9 1.0 NE2 A:HIS696 2.1 12.5 1.0 NE2 A:HIS660 2.1 12.3 1.0 CG A:ASP808 3.0 14.6 1.0 CE1 A:HIS660 3.0 12.1 1.0 CD2 A:HIS696 3.0 12.2 1.0 CE1 A:HIS696 3.1 12.4 1.0 CG A:ASP697 3.1 11.3 1.0 CD2 A:HIS660 3.1 12.1 1.0 OD2 A:ASP808 3.2 14.8 1.0 OD1 A:ASP697 3.7 11.1 1.0 MG A:MG1919 3.9 12.1 1.0 O A:HOH2063 4.1 11.6 1.0 CD2 A:HIS656 4.1 14.3 1.0 O A:HOH2061 4.1 13.8 1.0 ND1 A:HIS696 4.1 12.2 1.0 ND1 A:HIS660 4.2 11.8 1.0 CG A:HIS696 4.2 12.0 1.0 NE2 A:HIS656 4.2 14.6 1.0 CG A:HIS660 4.2 12.1 1.0 CB A:ASP697 4.3 11.2 1.0 CB A:ASP808 4.4 14.5 1.0 O A:HOH2075 4.8 11.5 1.0 CA A:ASP808 4.8 14.4 1.0 CG2 A:VAL664 4.9 12.3 1.0 O A:ASP808 4.9 14.3 1.0

Zinc binding site 2 out of 4 in the PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn1001 b:13.2 occ:1.00 OD2 B:ASP697 2.0 12.3 1.0 O B:HOH2061 2.0 12.3 1.0 OD1 B:ASP808 2.0 13.5 1.0 O B:HOH2049 2.0 12.8 1.0 NE2 B:HIS696 2.1 13.1 1.0 NE2 B:HIS660 2.1 12.5 1.0 CG B:ASP808 3.0 13.7 1.0 CD2 B:HIS696 3.0 13.0 1.0 CE1 B:HIS660 3.0 12.6 1.0 CE1 B:HIS696 3.1 13.2 1.0 CD2 B:HIS660 3.1 12.4 1.0 CG B:ASP697 3.1 12.0 1.0 OD2 B:ASP808 3.3 14.1 1.0 OD1 B:ASP697 3.7 11.8 1.0 MG B:MG1918 3.8 12.2 1.0 CD2 B:HIS656 4.1 14.5 1.0 O B:HOH2048 4.2 12.0 1.0 ND1 B:HIS696 4.2 13.2 1.0 ND1 B:HIS660 4.2 12.4 1.0 CG B:HIS696 4.2 12.9 1.0 O B:HOH2046 4.2 14.0 1.0 CG B:HIS660 4.2 12.6 1.0 NE2 B:HIS656 4.3 14.6 1.0 CB B:ASP697 4.3 12.0 1.0 CB B:ASP808 4.4 13.5 1.0 O B:HOH2060 4.8 11.9 1.0 CA B:ASP808 4.9 13.2 1.0 CG2 B:VAL664 4.9 12.2 1.0 O B:ASP808 4.9 12.6 1.0 C29 B:Q2T1917 5.0 15.3 1.0

Zinc binding site 3 out of 4 in the PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn1001 b:14.2 occ:1.00 O C:HOH2032 2.0 13.7 1.0 OD2 C:ASP697 2.0 13.3 1.0 OD1 C:ASP808 2.0 13.9 1.0 O C:HOH2038 2.0 12.3 1.0 NE2 C:HIS696 2.1 14.1 1.0 NE2 C:HIS660 2.1 13.7 1.0 CG C:ASP808 2.9 14.8 1.0 CD2 C:HIS696 3.0 14.0 1.0 CD2 C:HIS660 3.1 14.0 1.0 CE1 C:HIS660 3.1 13.8 1.0 CE1 C:HIS696 3.1 14.1 1.0 OD2 C:ASP808 3.1 14.7 1.0 CG C:ASP697 3.1 13.1 1.0 OD1 C:ASP697 3.7 12.2 1.0 MG C:MG1918 3.8 11.6 1.0 O C:HOH2031 4.0 11.0 1.0 CD2 C:HIS656 4.1 14.4 1.0 O C:HOH2030 4.1 19.0 1.0 NE2 C:HIS656 4.2 14.6 1.0 CG C:HIS696 4.2 14.1 1.0 ND1 C:HIS696 4.2 14.1 1.0 ND1 C:HIS660 4.2 13.9 1.0 CG C:HIS660 4.2 14.2 1.0 CB C:ASP697 4.3 13.0 1.0 CB C:ASP808 4.4 15.1 1.0 O C:HOH2037 4.7 11.9 1.0 CA C:ASP808 4.8 15.5 1.0 C29 C:Q2T1917 4.9 16.2 1.0 O C:ASP808 4.9 14.8 1.0 CG2 C:VAL664 4.9 13.3 1.0 O28 C:Q2T1917 5.0 15.8 1.0

Zinc binding site 4 out of 4 in the PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 4 of PDE2A Catalytic Domain in Complex with A Brain Penetrant Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ D:Zn1001 b:13.3 occ:1.00 OD2 D:ASP697 2.0 12.4 1.0 O D:HOH2042 2.0 12.2 1.0 O D:HOH2031 2.0 13.6 1.0 OD1 D:ASP808 2.0 12.9 1.0 NE2 D:HIS696 2.1 12.9 1.0 NE2 D:HIS660 2.1 13.1 1.0 CG D:ASP808 2.9 13.6 1.0 CD2 D:HIS696 3.0 12.8 1.0 CE1 D:HIS660 3.1 13.0 1.0 CD2 D:HIS660 3.1 13.3 1.0 CE1 D:HIS696 3.1 12.8 1.0 CG D:ASP697 3.1 12.3 1.0 OD2 D:ASP808 3.1 13.3 1.0 OD1 D:ASP697 3.7 11.8 1.0 MG D:MG1923 3.8 11.8 1.0 O D:HOH2030 4.0 11.2 1.0 CD2 D:HIS656 4.1 14.5 1.0 O D:HOH2029 4.2 18.6 1.0 ND1 D:HIS696 4.2 12.8 1.0 CG D:HIS696 4.2 12.8 1.0 ND1 D:HIS660 4.2 13.0 1.0 CG D:HIS660 4.2 13.2 1.0 CB D:ASP697 4.3 12.3 1.0 NE2 D:HIS656 4.4 14.6 1.0 CB D:ASP808 4.4 13.4 1.0 O D:HOH2041 4.7 12.4 1.0 CG2 D:VAL664 4.9 13.2 1.0 CA D:ASP808 4.9 13.6 1.0 C29 D:Q2T1922 5.0 15.7 1.0 O28 D:Q2T1922 5.0 15.8 1.0

P.Buijnsters, M.De Angelis, X.Langlois, F.J.R.Rombouts, W.Sanderson, G.Tresadern, A.Ritchie, A.A.Trabanco, G.Vanhoof, Y.V.Roosbroeck, J.Andres. Structure-Based Design of A Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement. Acs Med.Chem.Lett. V. 5 1049 2014.
ISSN: ISSN 1948-5875
PubMed: 25221665
DOI: 10.1021/ML500262U