Zinc in PDB 6htt: Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7
Enzymatic activity of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7
All present enzymatic activity of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7:
3.5.1.98;
Protein crystallography data
The structure of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7, PDB code: 6htt
was solved by
T.B.Shaik,
M.Marek,
C.Romier,
with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:
Resolution Low / High (Å)
|
47.82 /
1.75
|
Space group
|
P 1
|
Cell size a, b, c (Å), α, β, γ (°)
|
70.400,
70.500,
98.330,
75.80,
77.71,
85.53
|
R / Rfree (%)
|
15 /
18.3
|
Other elements in 6htt:
The structure of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7 also contains other interesting chemical elements:
Zinc Binding Sites:
The binding sites of Zinc atom in the Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7
(pdb code 6htt). This binding sites where shown within
5.0 Angstroms radius around Zinc atom.
In total 4 binding sites of Zinc where determined in the
Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7, PDB code: 6htt:
Jump to Zinc binding site number:
1;
2;
3;
4;
Zinc binding site 1 out
of 4 in 6htt
Go back to
Zinc Binding Sites List in 6htt
Zinc binding site 1 out
of 4 in the Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7
Mono view
Stereo pair view
|
A full contact list of Zinc with other atoms in the Zn binding
site number 1 of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:Zn501
b:21.1
occ:1.00
|
OD1
|
A:ASP186
|
2.0
|
15.7
|
1.0
|
OD2
|
A:ASP285
|
2.0
|
16.2
|
1.0
|
ND1
|
A:HIS188
|
2.1
|
12.8
|
1.0
|
O19
|
A:GQZ504
|
2.2
|
20.3
|
1.0
|
O17
|
A:GQZ504
|
2.2
|
22.7
|
1.0
|
C15
|
A:GQZ504
|
2.7
|
28.9
|
1.0
|
N16
|
A:GQZ504
|
2.7
|
31.4
|
1.0
|
CG
|
A:ASP186
|
2.8
|
19.7
|
1.0
|
CE1
|
A:HIS188
|
3.0
|
17.5
|
1.0
|
CG
|
A:ASP285
|
3.0
|
21.2
|
1.0
|
OD2
|
A:ASP186
|
3.1
|
16.6
|
1.0
|
CG
|
A:HIS188
|
3.2
|
16.7
|
1.0
|
OD1
|
A:ASP285
|
3.4
|
19.4
|
1.0
|
CB
|
A:HIS188
|
3.6
|
12.2
|
1.0
|
N
|
A:HIS188
|
3.8
|
13.6
|
1.0
|
C10
|
A:GQZ504
|
4.0
|
26.1
|
1.0
|
CA
|
A:GLY339
|
4.1
|
19.4
|
1.0
|
NE2
|
A:HIS188
|
4.1
|
16.1
|
1.0
|
O
|
A:HOH716
|
4.2
|
32.4
|
1.0
|
CD2
|
A:HIS188
|
4.3
|
13.0
|
1.0
|
CB
|
A:ASP186
|
4.3
|
13.7
|
1.0
|
N
|
A:LEU187
|
4.3
|
13.2
|
1.0
|
CB
|
A:ASP285
|
4.3
|
16.7
|
1.0
|
CA
|
A:HIS188
|
4.4
|
11.6
|
1.0
|
OH
|
A:TYR341
|
4.4
|
21.0
|
1.0
|
NE2
|
A:HIS141
|
4.4
|
19.3
|
1.0
|
N
|
A:GLY339
|
4.5
|
18.2
|
1.0
|
CB
|
A:LEU187
|
4.5
|
15.0
|
1.0
|
CE2
|
A:TYR341
|
4.6
|
18.5
|
1.0
|
C11
|
A:GQZ504
|
4.7
|
22.6
|
1.0
|
C
|
A:LEU187
|
4.7
|
13.5
|
1.0
|
CA
|
A:LEU187
|
4.7
|
16.4
|
1.0
|
CE1
|
A:HIS141
|
4.8
|
16.3
|
1.0
|
NE2
|
A:HIS142
|
4.9
|
16.1
|
1.0
|
C
|
A:ASP186
|
5.0
|
16.2
|
1.0
|
|
Zinc binding site 2 out
of 4 in 6htt
Go back to
Zinc Binding Sites List in 6htt
Zinc binding site 2 out
of 4 in the Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7
Mono view
Stereo pair view
|
A full contact list of Zinc with other atoms in the Zn binding
site number 2 of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:Zn501
b:19.7
occ:1.00
|
OD1
|
B:ASP186
|
1.9
|
10.6
|
1.0
|
OD2
|
B:ASP285
|
2.0
|
12.9
|
1.0
|
O19
|
B:GQZ504
|
2.2
|
18.3
|
1.0
|
ND1
|
B:HIS188
|
2.2
|
13.7
|
1.0
|
O17
|
B:GQZ504
|
2.2
|
21.1
|
1.0
|
C15
|
B:GQZ504
|
2.7
|
24.9
|
1.0
|
N16
|
B:GQZ504
|
2.7
|
27.3
|
1.0
|
CG
|
B:ASP186
|
2.8
|
12.9
|
1.0
|
OD2
|
B:ASP186
|
3.0
|
14.7
|
1.0
|
CE1
|
B:HIS188
|
3.0
|
17.3
|
1.0
|
CG
|
B:ASP285
|
3.0
|
16.0
|
1.0
|
CG
|
B:HIS188
|
3.2
|
12.3
|
1.0
|
OD1
|
B:ASP285
|
3.4
|
14.2
|
1.0
|
CB
|
B:HIS188
|
3.6
|
10.3
|
1.0
|
N
|
B:HIS188
|
3.9
|
12.8
|
1.0
|
C10
|
B:GQZ504
|
4.1
|
23.1
|
1.0
|
CA
|
B:GLY339
|
4.1
|
9.4
|
1.0
|
NE2
|
B:HIS188
|
4.2
|
14.7
|
1.0
|
CB
|
B:ASP186
|
4.2
|
11.1
|
1.0
|
O
|
B:HOH777
|
4.3
|
41.1
|
1.0
|
CD2
|
B:HIS188
|
4.3
|
13.6
|
1.0
|
N
|
B:LEU187
|
4.3
|
11.3
|
1.0
|
CB
|
B:ASP285
|
4.4
|
12.0
|
1.0
|
NE2
|
B:HIS141
|
4.4
|
16.4
|
1.0
|
CA
|
B:HIS188
|
4.4
|
11.1
|
1.0
|
N
|
B:GLY339
|
4.5
|
12.8
|
1.0
|
OH
|
B:TYR341
|
4.5
|
18.2
|
1.0
|
CB
|
B:LEU187
|
4.5
|
11.3
|
1.0
|
CE2
|
B:TYR341
|
4.7
|
14.6
|
1.0
|
C11
|
B:GQZ504
|
4.7
|
22.6
|
1.0
|
CE1
|
B:HIS141
|
4.7
|
12.2
|
1.0
|
C
|
B:LEU187
|
4.7
|
14.5
|
1.0
|
CA
|
B:LEU187
|
4.8
|
10.4
|
1.0
|
NE2
|
B:HIS142
|
4.9
|
18.1
|
1.0
|
C
|
B:ASP186
|
5.0
|
12.3
|
1.0
|
CA
|
B:ASP186
|
5.0
|
10.4
|
1.0
|
|
Zinc binding site 3 out
of 4 in 6htt
Go back to
Zinc Binding Sites List in 6htt
Zinc binding site 3 out
of 4 in the Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7
Mono view
Stereo pair view
|
A full contact list of Zinc with other atoms in the Zn binding
site number 3 of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
C:Zn501
b:20.7
occ:1.00
|
OD1
|
C:ASP186
|
1.9
|
14.0
|
1.0
|
OD2
|
C:ASP285
|
2.0
|
14.9
|
1.0
|
O19
|
C:GQZ504
|
2.1
|
19.0
|
1.0
|
ND1
|
C:HIS188
|
2.1
|
14.6
|
1.0
|
O17
|
C:GQZ504
|
2.2
|
20.4
|
1.0
|
C15
|
C:GQZ504
|
2.7
|
25.9
|
1.0
|
N16
|
C:GQZ504
|
2.8
|
30.9
|
1.0
|
CG
|
C:ASP186
|
2.8
|
14.0
|
1.0
|
CE1
|
C:HIS188
|
3.0
|
18.8
|
1.0
|
CG
|
C:ASP285
|
3.0
|
16.6
|
1.0
|
OD2
|
C:ASP186
|
3.1
|
13.5
|
1.0
|
CG
|
C:HIS188
|
3.2
|
13.0
|
1.0
|
OD1
|
C:ASP285
|
3.4
|
14.2
|
1.0
|
CB
|
C:HIS188
|
3.7
|
13.3
|
1.0
|
N
|
C:HIS188
|
3.8
|
13.2
|
1.0
|
C10
|
C:GQZ504
|
4.0
|
28.3
|
1.0
|
CA
|
C:GLY339
|
4.1
|
15.0
|
1.0
|
NE2
|
C:HIS188
|
4.1
|
13.4
|
1.0
|
CB
|
C:ASP186
|
4.3
|
11.7
|
1.0
|
CD2
|
C:HIS188
|
4.3
|
12.6
|
1.0
|
CB
|
C:ASP285
|
4.3
|
15.0
|
1.0
|
N
|
C:LEU187
|
4.3
|
10.3
|
1.0
|
O
|
C:HOH727
|
4.4
|
35.1
|
1.0
|
CA
|
C:HIS188
|
4.4
|
11.4
|
1.0
|
NE2
|
C:HIS141
|
4.4
|
18.3
|
1.0
|
OH
|
C:TYR341
|
4.4
|
18.0
|
1.0
|
N
|
C:GLY339
|
4.4
|
13.5
|
1.0
|
CB
|
C:LEU187
|
4.5
|
11.6
|
1.0
|
CE2
|
C:TYR341
|
4.6
|
16.5
|
1.0
|
C11
|
C:GQZ504
|
4.7
|
21.8
|
1.0
|
C
|
C:LEU187
|
4.7
|
16.9
|
1.0
|
CA
|
C:LEU187
|
4.7
|
13.5
|
1.0
|
CE1
|
C:HIS141
|
4.8
|
16.5
|
1.0
|
NE2
|
C:HIS142
|
4.9
|
18.7
|
1.0
|
C
|
C:ASP186
|
5.0
|
10.1
|
1.0
|
|
Zinc binding site 4 out
of 4 in 6htt
Go back to
Zinc Binding Sites List in 6htt
Zinc binding site 4 out
of 4 in the Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7
Mono view
Stereo pair view
|
A full contact list of Zinc with other atoms in the Zn binding
site number 4 of Crystal Structure of Schistosoma Mansoni HDAC8 Complexed with A Benzohydroxamate Inhibitor 7 within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
D:Zn502
b:20.6
occ:1.00
|
OD2
|
D:ASP285
|
2.0
|
17.5
|
1.0
|
OD1
|
D:ASP186
|
2.0
|
13.4
|
1.0
|
ND1
|
D:HIS188
|
2.1
|
12.8
|
1.0
|
O17
|
D:GQZ505
|
2.1
|
19.8
|
1.0
|
O19
|
D:GQZ505
|
2.2
|
26.2
|
1.0
|
C15
|
D:GQZ505
|
2.7
|
32.1
|
1.0
|
N16
|
D:GQZ505
|
2.7
|
29.9
|
1.0
|
CG
|
D:ASP186
|
2.9
|
16.1
|
1.0
|
CE1
|
D:HIS188
|
2.9
|
21.8
|
1.0
|
CG
|
D:ASP285
|
3.0
|
14.0
|
1.0
|
OD2
|
D:ASP186
|
3.1
|
13.8
|
1.0
|
CG
|
D:HIS188
|
3.2
|
15.6
|
1.0
|
OD1
|
D:ASP285
|
3.4
|
16.6
|
1.0
|
CB
|
D:HIS188
|
3.6
|
15.6
|
1.0
|
N
|
D:HIS188
|
3.8
|
12.4
|
1.0
|
C10
|
D:GQZ505
|
4.1
|
26.9
|
1.0
|
NE2
|
D:HIS188
|
4.1
|
16.7
|
1.0
|
CA
|
D:GLY339
|
4.2
|
13.2
|
1.0
|
O
|
D:HOH779
|
4.2
|
37.2
|
1.0
|
CD2
|
D:HIS188
|
4.2
|
15.6
|
1.0
|
CB
|
D:ASP186
|
4.3
|
14.1
|
1.0
|
CB
|
D:ASP285
|
4.3
|
12.2
|
1.0
|
N
|
D:LEU187
|
4.3
|
11.5
|
1.0
|
CA
|
D:HIS188
|
4.4
|
12.8
|
1.0
|
OH
|
D:TYR341
|
4.4
|
17.3
|
1.0
|
NE2
|
D:HIS141
|
4.4
|
21.7
|
1.0
|
CB
|
D:LEU187
|
4.5
|
11.9
|
1.0
|
N
|
D:GLY339
|
4.5
|
16.5
|
1.0
|
CE2
|
D:TYR341
|
4.6
|
18.5
|
1.0
|
C
|
D:LEU187
|
4.7
|
15.2
|
1.0
|
C11
|
D:GQZ505
|
4.7
|
24.1
|
1.0
|
CA
|
D:LEU187
|
4.8
|
10.8
|
1.0
|
CE1
|
D:HIS141
|
4.8
|
17.3
|
1.0
|
NE2
|
D:HIS142
|
4.9
|
15.9
|
1.0
|
|
Reference:
M.Marek,
T.B.Shaik,
T.Heimburg,
A.Chakrabarti,
J.Lancelot,
E.Ramos-Morales,
C.Da Veiga,
D.Kalinin,
J.Melesina,
D.Robaa,
K.Schmidtkunz,
T.Suzuki,
R.Holl,
E.Ennifar,
R.J.Pierce,
M.Jung,
W.Sippl,
C.Romier.
Characterization of Histone Deacetylase 8 (HDAC8) Selective Inhibition Reveals Specific Active Site Structural and Functional Determinants. J. Med. Chem. V. 61 10000 2018.
ISSN: ISSN 1520-4804
PubMed: 30347148
DOI: 10.1021/ACS.JMEDCHEM.8B01087
Page generated: Mon Oct 28 23:18:19 2024
|