Zinc in PDB 7mos: Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4)

All present enzymatic activity of Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4):
3.5.1.98;

The structure of Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4), PDB code: 7mos was solved by D.J.Klein, W.Yu, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	80.75 / 1.70
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	92.447, 98.947, 139.708, 90, 90, 90
R / Rfree (%)	18.3 / 20.8

The structure of Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4) also contains other interesting chemical elements:

Calcium

(Ca)

6 atoms

The binding sites of Zinc atom in the Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4) (pdb code 7mos). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 3 binding sites of Zinc where determined in the Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4), PDB code: 7mos:
Jump to Zinc binding site number: 1; 2; 3;

Zinc binding site 1 out of 3 in the Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4)


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4) within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn401 b:17.1 occ:1.00 OD2 A:ASP265 1.9 15.1 1.0 OD1 A:ASP177 2.0 16.9 1.0 ND1 A:HIS179 2.1 16.6 1.0 O A:ZLV412 2.1 21.3 1.0 O1 A:ZLV412 2.5 19.4 1.0 C2 A:ZLV412 2.8 21.8 1.0 CG A:ASP177 2.8 16.1 1.0 CG A:ASP265 2.9 15.8 1.0 CE1 A:HIS179 3.0 17.4 1.0 OD2 A:ASP177 3.0 16.2 1.0 CG A:HIS179 3.2 15.8 1.0 OD1 A:ASP265 3.2 15.1 1.0 CB A:HIS179 3.6 15.6 1.0 C1 A:ZLV412 3.8 22.9 1.0 N A:HIS179 3.8 14.7 1.0 C3 A:ZLV412 3.9 22.0 1.0 C4 A:ZLV412 3.9 22.6 1.0 CA A:GLY302 4.1 17.3 1.0 CG2 A:ILE178 4.1 15.2 1.0 NE2 A:HIS179 4.2 18.2 1.0 CB A:ASP177 4.2 15.3 1.0 CB A:ASP265 4.2 16.3 1.0 CD2 A:HIS179 4.3 16.8 1.0 CA A:HIS179 4.3 15.4 1.0 N A:ILE178 4.4 14.5 1.0 NE2 A:HIS141 4.4 18.3 1.0 OH A:TYR304 4.4 16.4 1.0 CE2 A:TYR304 4.4 14.9 1.0 N A:GLY302 4.5 17.2 1.0 CE1 A:HIS141 4.8 18.2 1.0 C A:ILE178 4.8 15.6 1.0 C A:ZLV412 4.9 23.2 1.0 C A:ASP177 4.9 15.2 1.0 NE2 A:HIS142 4.9 17.9 1.0 CA A:ASP177 4.9 14.2 1.0 CZ A:TYR304 4.9 15.6 1.0 CA A:ILE178 5.0 14.6 1.0

Zinc binding site 2 out of 3 in the Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4)


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4) within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn401 b:15.6 occ:1.00 OD2 B:ASP265 1.9 16.0 1.0 OD1 B:ASP177 2.0 15.8 1.0 ND1 B:HIS179 2.0 13.4 1.0 O B:ZLV410 2.1 18.4 1.0 O1 B:ZLV410 2.5 17.7 1.0 C2 B:ZLV410 2.8 19.1 1.0 CG B:ASP177 2.8 16.5 1.0 CE1 B:HIS179 2.9 15.6 1.0 CG B:ASP265 2.9 15.3 1.0 OD2 B:ASP177 3.0 15.9 1.0 CG B:HIS179 3.1 14.1 1.0 OD1 B:ASP265 3.3 14.8 1.0 CB B:HIS179 3.6 13.5 1.0 N B:HIS179 3.8 13.7 1.0 C1 B:ZLV410 3.9 19.9 1.0 C3 B:ZLV410 3.9 19.0 1.0 C4 B:ZLV410 3.9 19.9 1.0 CA B:GLY302 4.0 15.0 1.0 NE2 B:HIS179 4.1 16.4 1.0 CG2 B:ILE178 4.2 14.8 1.0 CD2 B:HIS179 4.2 14.9 1.0 CB B:ASP177 4.2 13.3 1.0 CB B:ASP265 4.3 13.8 1.0 CA B:HIS179 4.3 13.7 1.0 N B:ILE178 4.3 12.6 1.0 NE2 B:HIS141 4.4 16.8 1.0 N B:GLY302 4.4 14.3 1.0 OH B:TYR304 4.4 16.8 1.0 CE2 B:TYR304 4.4 14.1 1.0 C B:ILE178 4.8 13.9 1.0 CE1 B:HIS141 4.8 17.3 1.0 C B:ZLV410 4.9 19.6 1.0 C B:ASP177 4.9 13.4 1.0 CA B:ASP177 4.9 13.1 1.0 NE2 B:HIS142 4.9 18.1 1.0 CZ B:TYR304 5.0 15.0 1.0 CA B:ILE178 5.0 12.8 1.0

Zinc binding site 3 out of 3 in the Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4)


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of Structure of HDAC2 in Complex with A Macrocyclic Inhibitor (Compound 4) within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn401 b:21.9 occ:1.00 OD2 C:ASP265 2.0 22.4 1.0 OD1 C:ASP177 2.0 17.4 1.0 ND1 C:HIS179 2.0 22.6 1.0 O C:ZLV410 2.2 24.4 1.0 O1 C:ZLV410 2.4 23.7 1.0 C2 C:ZLV410 2.8 25.4 1.0 CG C:ASP177 2.8 20.4 1.0 CG C:ASP265 2.9 23.1 1.0 CE1 C:HIS179 2.9 22.5 1.0 OD2 C:ASP177 3.0 22.8 1.0 CG C:HIS179 3.1 20.1 1.0 OD1 C:ASP265 3.2 22.0 1.0 CB C:HIS179 3.5 19.6 1.0 N C:HIS179 3.8 19.6 1.0 C1 C:ZLV410 3.9 26.0 1.0 C3 C:ZLV410 3.9 26.5 1.0 C4 C:ZLV410 3.9 27.6 1.0 CA C:GLY302 4.1 23.2 1.0 NE2 C:HIS179 4.1 21.9 1.0 CG2 C:ILE178 4.1 21.0 1.0 CD2 C:HIS179 4.2 21.1 1.0 CB C:ASP177 4.2 19.2 1.0 CB C:ASP265 4.3 22.2 1.0 CA C:HIS179 4.3 19.5 1.0 N C:ILE178 4.3 19.6 1.0 OH C:TYR304 4.3 25.4 1.0 NE2 C:HIS141 4.4 23.5 1.0 CE2 C:TYR304 4.5 25.4 1.0 N C:GLY302 4.5 22.7 1.0 C C:ILE178 4.8 19.3 1.0 CE1 C:HIS141 4.8 23.6 1.0 C C:ZLV410 4.9 26.2 1.0 NE2 C:HIS142 4.9 21.7 1.0 CZ C:TYR304 4.9 26.0 1.0 C C:ASP177 4.9 20.4 1.0 CA C:ILE178 4.9 19.5 1.0 CA C:ASP177 5.0 20.2 1.0

W.Yu, J.Fells, D.Clausen, J.Liu, D.J.Klein, C.Christine Chung, R.W.Myers, J.Wu, G.Wu, B.J.Howell, R.J.O.Barnard, J.Kozlowski. Discovery of Macrocyclic Hdacs 1, 2, and 3 Selective Inhibitors For Hiv Latency Reactivation. Bioorg.Med.Chem.Lett. V. 47 28168 2021.
ISSN: ESSN 1464-3405
PubMed: 34091041
DOI: 10.1016/J.BMCL.2021.128168