Zinc in PDB 8cj7: HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor

The structure of HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor, PDB code: 8cj7 was solved by J.Sandmark, M.Ek, L.Ripa, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	90.19 / 1.51
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	95.977, 84.062, 96.132, 90, 110.25, 90
R / Rfree (%)	20.6 / 22.7

The structure of HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor also contains other interesting chemical elements:

Potassium	(K)	6 atoms
Iodine	(I)	6 atoms

The binding sites of Zinc atom in the HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor (pdb code 8cj7). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 3 binding sites of Zinc where determined in the HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor, PDB code: 8cj7:
Jump to Zinc binding site number: 1; 2; 3;

Zinc binding site 1 out of 3 in the HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn803 b:41.4 occ:1.00 ND1 A:HIS614 2.0 11.2 1.0 OD2 A:ASP705 2.1 10.1 1.0 N21 A:UTO804 2.2 12.3 1.0 OD1 A:ASP612 2.2 7.7 1.0 O1 A:UTO804 2.6 14.6 1.0 OD2 A:ASP612 2.6 10.1 1.0 N20 A:UTO804 2.7 16.9 1.0 CG A:ASP612 2.7 8.3 1.0 C2 A:UTO804 2.9 15.0 1.0 CE1 A:HIS614 2.9 11.1 1.0 CG A:HIS614 3.1 10.1 1.0 CG A:ASP705 3.1 10.5 1.0 CB A:HIS614 3.5 8.0 1.0 OD1 A:ASP705 3.5 9.8 1.0 N A:HIS614 4.0 8.0 1.0 NE2 A:HIS614 4.1 10.7 1.0 CA A:GLY743 4.1 7.5 1.0 NE2 A:HIS573 4.1 7.7 1.0 C3 A:UTO804 4.1 16.0 1.0 CD2 A:HIS614 4.2 10.7 1.0 CB A:ASP612 4.2 5.1 1.0 CA A:HIS614 4.4 7.5 1.0 CB A:ASP705 4.4 8.6 1.0 CG1 A:VAL613 4.5 8.9 1.0 N A:VAL613 4.5 6.1 1.0 N A:GLY743 4.5 6.4 1.0 OH A:TYR745 4.5 11.9 1.0 NE2 A:HIS574 4.6 10.9 1.0 CE1 A:HIS573 4.6 7.5 1.0 C19 A:UTO804 4.6 17.4 1.0 CE2 A:TYR745 4.7 10.9 1.0 C A:ASP612 4.9 7.9 1.0 C A:VAL613 4.9 10.6 1.0 C A:GLY743 5.0 10.5 1.0 CA A:ASP612 5.0 5.9 1.0

Zinc binding site 2 out of 3 in the HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn803 b:51.3 occ:1.00 ND1 B:HIS614 2.0 14.4 1.0 N21 B:UTO804 2.1 4.7 0.5 OD2 B:ASP705 2.1 18.2 1.0 OD1 B:ASP612 2.2 10.3 1.0 O1 B:UTO804 2.5 26.5 0.5 N21 B:UTO804 2.6 26.5 0.5 O1 B:UTO804 2.6 11.1 0.5 N20 B:UTO804 2.6 10.8 0.5 OD2 B:ASP612 2.7 12.6 1.0 CG B:ASP612 2.8 10.0 1.0 C2 B:UTO804 2.9 11.8 0.5 CE1 B:HIS614 2.9 13.7 1.0 C2 B:UTO804 3.0 26.0 0.5 N20 B:UTO804 3.0 26.0 0.5 CG B:HIS614 3.1 13.4 1.0 CG B:ASP705 3.1 14.3 1.0 CB B:HIS614 3.5 10.8 1.0 OD1 B:ASP705 3.6 12.8 1.0 N B:HIS614 4.0 11.6 1.0 NE2 B:HIS614 4.1 13.8 1.0 NE2 B:HIS573 4.1 13.3 1.0 C3 B:UTO804 4.1 14.5 0.5 CD2 B:HIS614 4.2 14.0 1.0 CA B:GLY743 4.2 8.1 1.0 C3 B:UTO804 4.2 25.5 0.5 CB B:ASP612 4.3 6.9 1.0 CA B:HIS614 4.4 10.7 1.0 CB B:ASP705 4.4 13.2 1.0 CG1 B:VAL613 4.5 12.3 1.0 N B:VAL613 4.5 9.2 1.0 OH B:TYR745 4.5 19.5 1.0 N B:GLY743 4.5 7.4 1.0 NE2 B:HIS574 4.6 13.1 1.0 CE1 B:HIS573 4.6 12.6 1.0 C19 B:UTO804 4.6 17.2 0.5 C19 B:UTO804 4.7 25.9 0.5 CE2 B:TYR745 4.7 16.6 1.0 C B:ASP612 4.9 11.6 1.0 C B:VAL613 4.9 13.1 1.0 CA B:ASP612 5.0 7.1 1.0

Zinc binding site 3 out of 3 in the HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of HDAC6 Selective Degraded (Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn803 b:89.8 occ:1.00 ND1 C:HIS614 2.9 34.7 1.0 OD1 C:ASP612 3.1 28.4 1.0 OD2 C:ASP612 3.3 28.5 1.0 OD2 C:ASP705 3.4 35.7 1.0 NE2 C:HIS573 3.4 33.1 1.0 NE2 C:HIS574 3.5 36.6 1.0 CG C:ASP612 3.6 27.8 1.0 CG C:HIS614 3.6 33.6 1.0 CE1 C:HIS614 3.7 33.6 1.0 CB C:HIS614 3.9 30.9 1.0 OH C:TYR745 3.9 35.1 1.0 CA C:GLY743 4.1 22.0 1.0 CD2 C:HIS574 4.1 36.8 1.0 CE1 C:HIS573 4.2 32.8 1.0 N C:GLY743 4.4 22.6 1.0 CD2 C:HIS573 4.4 33.2 1.0 CG C:ASP705 4.5 27.7 1.0 CE1 C:HIS574 4.6 36.7 1.0 CD2 C:HIS614 4.6 34.1 1.0 NE2 C:HIS614 4.7 33.8 1.0 CE2 C:TYR745 4.8 25.6 1.0 CZ C:TYR745 4.8 34.2 1.0 OD1 C:ASP705 5.0 30.2 1.0

L.Ripa, J.Sandmark, G.Hughes, I.Shamovsky, A.Gunnarsson, J.Johansson, A.Llinas, M.Collins, B.Jung, A.Noven, N.Pemberton, M.Mogemark, Y.Xiong, Q.Li, S.Tangefjord, M.Ek, A.Astrand. Selective and Bioavailable HDAC6 2-(Difluoromethyl)-1,3,4-Oxadiazole Substrate Inhibitors and Modeling of Their Bioactivation Mechanism. J.Med.Chem. 2023.
ISSN: ISSN 0022-2623
PubMed: 37797307
DOI: 10.1021/ACS.JMEDCHEM.3C01269