Zinc in PDB 4d09: 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: 4d09 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)	19.77 / 2.50
Space group	P 1
Cell size a, b, c (Å), α, β, γ (°)	56.140, 73.430, 91.620, 109.37, 91.82, 91.05
R / Rfree (%)	20.642 / 27.746

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 4d09). 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: 4d09:
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:26.5 occ:1.00 OD2 A:ASP697 2.1 15.4 1.0 OD1 A:ASP808 2.2 20.1 1.0 NE2 A:HIS660 2.2 19.1 1.0 NE2 A:HIS696 2.3 15.6 1.0 O A:HOH2033 2.4 18.1 1.0 O A:HOH2043 2.4 9.4 1.0 CG A:ASP808 3.1 19.4 1.0 CE1 A:HIS660 3.1 18.9 1.0 CD2 A:HIS696 3.1 15.7 1.0 CD2 A:HIS660 3.2 19.0 1.0 CG A:ASP697 3.3 15.3 1.0 CE1 A:HIS696 3.3 15.7 1.0 OD2 A:ASP808 3.3 19.7 1.0 OD1 A:ASP697 3.8 14.3 1.0 O A:HOH2002 3.8 16.1 1.0 O A:HOH2034 3.9 17.0 1.0 MG A:MG1002 3.9 11.5 1.0 CD2 A:HIS656 4.0 20.3 1.0 NE2 A:HIS656 4.1 20.5 1.0 ND1 A:HIS660 4.3 19.2 1.0 CG A:HIS696 4.3 15.7 1.0 ND1 A:HIS696 4.3 15.7 1.0 CG A:HIS660 4.3 19.1 1.0 CB A:ASP808 4.5 19.2 1.0 CB A:ASP697 4.5 15.7 1.0 O A:HOH2042 4.6 25.5 1.0 CA A:ASP808 4.9 18.8 1.0 O A:ASP808 4.9 19.2 1.0 C27 A:7881 4.9 21.4 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:24.9 occ:1.00 OD2 B:ASP697 2.1 18.0 1.0 NE2 B:HIS696 2.1 20.8 1.0 OD1 B:ASP808 2.3 23.4 1.0 NE2 B:HIS660 2.4 16.8 1.0 O B:HOH2031 2.4 6.7 1.0 CE1 B:HIS696 3.1 21.2 1.0 CG B:ASP808 3.1 22.6 1.0 CG B:ASP697 3.2 18.5 1.0 CD2 B:HIS696 3.2 20.7 1.0 CD2 B:HIS660 3.2 16.6 1.0 OD2 B:ASP808 3.2 22.9 1.0 CE1 B:HIS660 3.4 16.3 1.0 OD1 B:ASP697 3.7 18.6 1.0 MG B:MG1002 3.9 14.3 1.0 O B:HOH2003 4.0 18.4 1.0 O B:HOH2029 4.0 5.7 1.0 CD2 B:HIS656 4.1 20.3 1.0 ND1 B:HIS696 4.2 20.8 1.0 NE2 B:HIS656 4.3 20.5 1.0 CG B:HIS696 4.3 20.5 1.0 CB B:ASP697 4.3 18.6 1.0 CG B:HIS660 4.4 16.9 1.0 ND1 B:HIS660 4.4 16.7 1.0 CB B:ASP808 4.5 21.4 1.0 O B:ASP808 4.9 20.4 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:26.2 occ:1.00 OD2 C:ASP697 2.0 22.7 1.0 OD1 C:ASP808 2.2 21.0 1.0 NE2 C:HIS696 2.3 26.9 1.0 NE2 C:HIS660 2.4 21.9 1.0 O C:HOH2005 2.5 28.1 1.0 CG C:ASP808 3.0 21.6 1.0 CD2 C:HIS696 3.0 26.6 1.0 OD2 C:ASP808 3.1 22.0 1.0 CG C:ASP697 3.1 22.3 1.0 CD2 C:HIS660 3.3 21.8 1.0 CE1 C:HIS696 3.4 27.4 1.0 CE1 C:HIS660 3.5 21.9 1.0 OD1 C:ASP697 3.6 21.8 1.0 O C:HOH2010 3.7 16.5 1.0 CD2 C:HIS656 4.2 25.7 1.0 CG C:HIS696 4.2 26.7 1.0 MG C:MG1002 4.3 28.3 1.0 CB C:ASP697 4.4 22.4 1.0 CB C:ASP808 4.4 21.6 1.0 ND1 C:HIS696 4.4 26.9 1.0 NE2 C:HIS656 4.5 25.4 1.0 CG C:HIS660 4.5 22.3 1.0 ND1 C:HIS660 4.6 22.2 1.0 O C:HOH2008 4.8 13.6 1.0 CA C:ASP808 4.9 22.2 1.0 O C:ASP808 4.9 21.6 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:28.0 occ:1.00 OD2 D:ASP697 2.0 23.3 1.0 OD1 D:ASP808 2.1 26.0 1.0 NE2 D:HIS696 2.3 26.6 1.0 O D:HOH2016 2.4 21.9 1.0 NE2 D:HIS660 2.4 25.4 1.0 O D:HOH2024 2.6 10.1 1.0 CG D:ASP808 2.9 25.5 1.0 CD2 D:HIS696 3.0 26.4 1.0 OD2 D:ASP808 3.0 25.8 1.0 CG D:ASP697 3.0 24.0 1.0 CD2 D:HIS660 3.3 25.6 1.0 CE1 D:HIS660 3.4 25.7 1.0 CE1 D:HIS696 3.4 26.6 1.0 OD1 D:ASP697 3.5 24.1 1.0 O D:HOH2015 3.8 20.0 1.0 O D:HOH2001 4.0 21.7 1.0 CG D:HIS696 4.2 25.7 1.0 CD2 D:HIS656 4.2 26.3 1.0 CB D:ASP697 4.3 24.3 1.0 CB D:ASP808 4.4 24.0 1.0 ND1 D:HIS696 4.4 25.8 1.0 NE2 D:HIS656 4.4 25.9 1.0 CG D:HIS660 4.5 25.5 1.0 ND1 D:HIS660 4.5 25.8 1.0 O D:HOH2023 4.7 21.7 1.0 MG D:MG1002 4.7 21.8 1.0 CA D:ASP808 4.8 23.3 1.0 C27 D:7881 5.0 25.3 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