Manganese in PDB 8oxg: Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate
Enzymatic activity of Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate
All present enzymatic activity of Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate:
3.4.11.18;
Protein crystallography data
The structure of Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate, PDB code: 8oxg
was solved by
S.Moss,
P.Cornelius,
with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:
Resolution Low / High (Å)
|
44.84 /
1.73
|
Space group
|
C 1 2 1
|
Cell size a, b, c (Å), α, β, γ (°)
|
119.05,
101.127,
83.737,
90,
98.76,
90
|
R / Rfree (%)
|
18.1 /
21.5
|
Manganese Binding Sites:
The binding sites of Manganese atom in the Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate
(pdb code 8oxg). This binding sites where shown within
5.0 Angstroms radius around Manganese atom.
In total 4 binding sites of Manganese where determined in the
Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate, PDB code: 8oxg:
Jump to Manganese binding site number:
1;
2;
3;
4;
Manganese binding site 1 out
of 4 in 8oxg
Go back to
Manganese Binding Sites List in 8oxg
Manganese binding site 1 out
of 4 in the Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate
Mono view
Stereo pair view
|
A full contact list of Manganese with other atoms in the Mn binding
site number 1 of Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:Mn502
b:18.6
occ:1.00
|
O
|
A:HOH676
|
2.0
|
24.1
|
1.0
|
OD1
|
A:ASP262
|
2.1
|
16.9
|
1.0
|
OD2
|
A:ASP251
|
2.1
|
21.1
|
1.0
|
OE1
|
A:GLU459
|
2.1
|
19.2
|
1.0
|
O
|
A:HOH812
|
2.2
|
18.4
|
1.0
|
OD1
|
A:ASP251
|
2.2
|
21.2
|
1.0
|
CG
|
A:ASP251
|
2.5
|
19.6
|
1.0
|
CD
|
A:GLU459
|
3.0
|
21.3
|
1.0
|
CG
|
A:ASP262
|
3.0
|
20.3
|
1.0
|
OE2
|
A:GLU459
|
3.2
|
19.6
|
1.0
|
HE22
|
A:GLN457
|
3.3
|
18.0
|
0.0
|
OD2
|
A:ASP262
|
3.3
|
20.6
|
1.0
|
MN
|
A:MN503
|
3.3
|
19.6
|
1.0
|
HZ
|
A:PHE219
|
3.7
|
21.6
|
1.0
|
HB2
|
A:ALA264
|
3.8
|
19.2
|
1.0
|
O
|
A:HOH728
|
3.9
|
23.2
|
1.0
|
H22
|
A:W5N501
|
3.9
|
20.1
|
0.0
|
OE1
|
A:GLU364
|
4.0
|
19.9
|
1.0
|
CB
|
A:ASP251
|
4.0
|
18.8
|
1.0
|
NE2
|
A:GLN457
|
4.0
|
18.0
|
1.0
|
O
|
A:HOH860
|
4.1
|
30.2
|
1.0
|
O
|
A:HOH743
|
4.1
|
25.9
|
1.0
|
HE21
|
A:GLN457
|
4.2
|
18.0
|
0.0
|
CZ
|
A:PHE219
|
4.2
|
22.2
|
1.0
|
HE1
|
A:PHE219
|
4.2
|
21.2
|
1.0
|
O3
|
A:W5N501
|
4.3
|
20.4
|
1.0
|
H
|
A:CYS263
|
4.3
|
20.9
|
1.0
|
CB
|
A:ASP262
|
4.4
|
22.0
|
1.0
|
HB3
|
A:ASP251
|
4.4
|
19.0
|
1.0
|
CG
|
A:GLU459
|
4.4
|
18.1
|
1.0
|
HB2
|
A:ASP251
|
4.4
|
19.0
|
1.0
|
HE2
|
A:HIS331
|
4.4
|
15.4
|
0.0
|
CE1
|
A:PHE219
|
4.4
|
21.9
|
1.0
|
N
|
A:CYS263
|
4.5
|
20.4
|
1.0
|
HA
|
A:ASP262
|
4.5
|
21.8
|
1.0
|
C
|
A:ASP262
|
4.6
|
20.7
|
1.0
|
HB3
|
A:GLU459
|
4.6
|
18.3
|
1.0
|
OE2
|
A:GLU364
|
4.7
|
23.1
|
1.0
|
HG2
|
A:GLU459
|
4.7
|
18.9
|
1.0
|
CD
|
A:GLU364
|
4.7
|
22.9
|
1.0
|
CB
|
A:ALA264
|
4.7
|
19.3
|
1.0
|
CA
|
A:ASP262
|
4.7
|
22.8
|
1.0
|
H20
|
A:W5N501
|
4.8
|
18.5
|
1.0
|
HB3
|
A:ASP262
|
4.8
|
21.8
|
1.0
|
HA
|
A:ASP251
|
4.8
|
19.3
|
1.0
|
HB2
|
A:GLU459
|
4.9
|
18.3
|
1.0
|
CB
|
A:GLU459
|
4.9
|
18.4
|
1.0
|
CA
|
A:ASP251
|
4.9
|
18.7
|
1.0
|
H24
|
A:W5N501
|
4.9
|
21.2
|
1.0
|
HB1
|
A:ALA264
|
5.0
|
19.2
|
1.0
|
HB2
|
A:ASP262
|
5.0
|
21.8
|
1.0
|
|
Manganese binding site 2 out
of 4 in 8oxg
Go back to
Manganese Binding Sites List in 8oxg
Manganese binding site 2 out
of 4 in the Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate
Mono view
Stereo pair view
|
A full contact list of Manganese with other atoms in the Mn binding
site number 2 of Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
A:Mn503
b:19.6
occ:1.00
|
HE2
|
A:HIS331
|
1.2
|
15.4
|
0.0
|
NE2
|
A:HIS331
|
2.1
|
15.4
|
1.0
|
O
|
A:HOH676
|
2.1
|
24.1
|
1.0
|
OE2
|
A:GLU459
|
2.1
|
19.6
|
1.0
|
OD2
|
A:ASP262
|
2.2
|
20.6
|
1.0
|
OE2
|
A:GLU364
|
2.2
|
23.1
|
1.0
|
HB1
|
A:ALA362
|
2.9
|
20.0
|
1.0
|
CG
|
A:ASP262
|
3.0
|
20.3
|
1.0
|
H22
|
A:W5N501
|
3.0
|
20.1
|
0.0
|
CE1
|
A:HIS331
|
3.0
|
21.4
|
1.0
|
CD
|
A:GLU364
|
3.0
|
22.9
|
1.0
|
CD2
|
A:HIS331
|
3.1
|
18.1
|
1.0
|
CD
|
A:GLU459
|
3.2
|
21.3
|
1.0
|
HE1
|
A:HIS331
|
3.2
|
18.2
|
1.0
|
OE1
|
A:GLU364
|
3.3
|
19.9
|
1.0
|
HD2
|
A:HIS331
|
3.3
|
17.0
|
1.0
|
MN
|
A:MN502
|
3.3
|
18.6
|
1.0
|
O3
|
A:W5N501
|
3.4
|
20.4
|
1.0
|
OD1
|
A:ASP262
|
3.4
|
16.9
|
1.0
|
HB2
|
A:ALA362
|
3.4
|
20.0
|
1.0
|
CB
|
A:ALA362
|
3.5
|
20.1
|
1.0
|
OE1
|
A:GLU459
|
3.6
|
19.2
|
1.0
|
O
|
A:HOH728
|
3.7
|
23.2
|
1.0
|
HB3
|
A:ALA362
|
3.7
|
20.0
|
1.0
|
H26
|
A:W5N501
|
4.0
|
21.4
|
1.0
|
H6
|
A:W5N501
|
4.0
|
17.6
|
1.0
|
HB3
|
A:ASP262
|
4.1
|
21.8
|
1.0
|
ND1
|
A:HIS331
|
4.2
|
15.0
|
1.0
|
CG
|
A:HIS331
|
4.2
|
16.0
|
1.0
|
CB
|
A:ASP262
|
4.2
|
22.0
|
1.0
|
H4
|
A:W5N501
|
4.2
|
20.0
|
1.0
|
O
|
A:HOH812
|
4.3
|
18.4
|
1.0
|
CG
|
A:GLU364
|
4.3
|
23.0
|
1.0
|
HG2
|
A:GLU364
|
4.3
|
22.8
|
1.0
|
HB3
|
A:GLU364
|
4.3
|
22.6
|
1.0
|
HA2
|
A:GLY330
|
4.4
|
19.3
|
1.0
|
CG
|
A:GLU459
|
4.5
|
18.1
|
1.0
|
HG3
|
A:GLU459
|
4.5
|
18.9
|
1.0
|
HB2
|
A:ASP262
|
4.7
|
21.8
|
1.0
|
C12
|
A:W5N501
|
4.8
|
19.5
|
1.0
|
C15
|
A:W5N501
|
4.9
|
22.2
|
1.0
|
CB
|
A:GLU364
|
4.9
|
22.2
|
1.0
|
C5
|
A:W5N501
|
4.9
|
16.6
|
1.0
|
HD1
|
A:HIS331
|
4.9
|
15.0
|
0.0
|
CA
|
A:ALA362
|
5.0
|
19.8
|
1.0
|
H24
|
A:W5N501
|
5.0
|
21.2
|
1.0
|
HG2
|
A:GLU459
|
5.0
|
18.9
|
1.0
|
H7
|
A:W5N501
|
5.0
|
17.6
|
1.0
|
OD2
|
A:ASP251
|
5.0
|
21.1
|
1.0
|
HD13
|
A:ILE338
|
5.0
|
28.0
|
1.0
|
|
Manganese binding site 3 out
of 4 in 8oxg
Go back to
Manganese Binding Sites List in 8oxg
Manganese binding site 3 out
of 4 in the Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate
Mono view
Stereo pair view
|
A full contact list of Manganese with other atoms in the Mn binding
site number 3 of Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:Mn502
b:19.1
occ:1.00
|
OD1
|
B:ASP262
|
2.0
|
19.7
|
1.0
|
OD2
|
B:ASP251
|
2.1
|
21.5
|
1.0
|
OE1
|
B:GLU459
|
2.1
|
19.6
|
1.0
|
O
|
B:HOH788
|
2.1
|
20.3
|
1.0
|
O
|
B:HOH634
|
2.1
|
24.5
|
1.0
|
OD1
|
B:ASP251
|
2.3
|
21.1
|
1.0
|
CG
|
B:ASP251
|
2.5
|
19.6
|
1.0
|
CD
|
B:GLU459
|
3.0
|
19.3
|
1.0
|
CG
|
B:ASP262
|
3.0
|
20.6
|
1.0
|
MN
|
B:MN503
|
3.3
|
21.6
|
1.0
|
OE2
|
B:GLU459
|
3.3
|
19.1
|
1.0
|
HE22
|
B:GLN457
|
3.3
|
16.9
|
0.0
|
OD2
|
B:ASP262
|
3.4
|
22.6
|
1.0
|
HZ
|
B:PHE219
|
3.6
|
18.7
|
1.0
|
HB2
|
B:ALA264
|
3.8
|
19.7
|
1.0
|
O
|
B:HOH728
|
3.9
|
29.7
|
1.0
|
H22
|
B:W5N501
|
3.9
|
18.6
|
0.0
|
OE1
|
B:GLU364
|
4.0
|
24.5
|
1.0
|
CB
|
B:ASP251
|
4.0
|
20.1
|
1.0
|
NE2
|
B:GLN457
|
4.0
|
17.0
|
1.0
|
O
|
B:HOH659
|
4.0
|
26.7
|
1.0
|
CZ
|
B:PHE219
|
4.1
|
17.9
|
1.0
|
O
|
B:HOH832
|
4.1
|
41.0
|
1.0
|
HE21
|
B:GLN457
|
4.1
|
16.9
|
0.0
|
HE1
|
B:PHE219
|
4.2
|
19.4
|
1.0
|
O3
|
B:W5N501
|
4.3
|
18.5
|
1.0
|
HB3
|
B:ASP251
|
4.4
|
19.9
|
1.0
|
CB
|
B:ASP262
|
4.4
|
17.7
|
1.0
|
H
|
B:CYS263
|
4.4
|
19.1
|
1.0
|
HB2
|
B:ASP251
|
4.4
|
19.9
|
1.0
|
CG
|
B:GLU459
|
4.4
|
16.3
|
1.0
|
CE1
|
B:PHE219
|
4.4
|
20.2
|
1.0
|
HE2
|
B:HIS331
|
4.4
|
19.9
|
1.0
|
HA
|
B:ASP262
|
4.5
|
18.5
|
1.0
|
N
|
B:CYS263
|
4.6
|
18.7
|
1.0
|
HB3
|
B:GLU459
|
4.6
|
16.3
|
1.0
|
CD
|
B:GLU364
|
4.7
|
22.7
|
1.0
|
HG2
|
B:GLU459
|
4.7
|
16.8
|
1.0
|
OE2
|
B:GLU364
|
4.7
|
25.1
|
1.0
|
CB
|
B:ALA264
|
4.7
|
20.4
|
1.0
|
C
|
B:ASP262
|
4.7
|
18.8
|
1.0
|
CA
|
B:ASP262
|
4.8
|
18.1
|
1.0
|
HB2
|
B:GLU459
|
4.8
|
16.3
|
1.0
|
HA
|
B:ASP251
|
4.8
|
19.8
|
1.0
|
HB3
|
B:ASP262
|
4.8
|
18.4
|
1.0
|
CB
|
B:GLU459
|
4.9
|
15.7
|
1.0
|
CA
|
B:ASP251
|
4.9
|
19.8
|
1.0
|
CE2
|
B:PHE219
|
5.0
|
18.8
|
1.0
|
HB1
|
B:ALA264
|
5.0
|
19.7
|
1.0
|
HB2
|
B:ASP262
|
5.0
|
18.4
|
1.0
|
H24
|
B:W5N501
|
5.0
|
24.9
|
1.0
|
|
Manganese binding site 4 out
of 4 in 8oxg
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Manganese Binding Sites List in 8oxg
Manganese binding site 4 out
of 4 in the Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate
Mono view
Stereo pair view
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A full contact list of Manganese with other atoms in the Mn binding
site number 4 of Crystal Structure of Human Methionine Aminopeptidase-2 Complexed with (3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-Methyl-3-(3-Methyl-2-Buten-1- Yl)-2-Oxiranyl]-1-Oxaspiro[2.5]Oct-6-Yl N-(Trans-4-Aminocyclohexyl) Carbamate within 5.0Å range:
probe
|
atom
|
residue
|
distance (Å)
|
B
|
Occ
|
B:Mn503
b:21.6
occ:1.00
|
HE2
|
B:HIS331
|
1.4
|
19.9
|
1.0
|
O
|
B:HOH634
|
2.0
|
24.5
|
1.0
|
OE2
|
B:GLU459
|
2.1
|
19.1
|
1.0
|
NE2
|
B:HIS331
|
2.2
|
17.9
|
1.0
|
OE2
|
B:GLU364
|
2.2
|
25.1
|
1.0
|
OD2
|
B:ASP262
|
2.2
|
22.6
|
1.0
|
CG
|
B:ASP262
|
3.0
|
20.6
|
1.0
|
HB1
|
B:ALA362
|
3.0
|
19.7
|
1.0
|
H22
|
B:W5N501
|
3.0
|
18.6
|
0.0
|
CD
|
B:GLU364
|
3.1
|
22.7
|
1.0
|
CD
|
B:GLU459
|
3.1
|
19.3
|
1.0
|
CD2
|
B:HIS331
|
3.1
|
22.4
|
1.0
|
CE1
|
B:HIS331
|
3.2
|
21.7
|
1.0
|
OD1
|
B:ASP262
|
3.3
|
19.7
|
1.0
|
MN
|
B:MN502
|
3.3
|
19.1
|
1.0
|
HD2
|
B:HIS331
|
3.3
|
20.9
|
1.0
|
HE1
|
B:HIS331
|
3.4
|
20.9
|
1.0
|
OE1
|
B:GLU364
|
3.4
|
24.5
|
1.0
|
O3
|
B:W5N501
|
3.4
|
18.5
|
1.0
|
OE1
|
B:GLU459
|
3.5
|
19.6
|
1.0
|
HB2
|
B:ALA362
|
3.5
|
19.7
|
1.0
|
CB
|
B:ALA362
|
3.6
|
19.5
|
1.0
|
O
|
B:HOH728
|
3.7
|
29.7
|
1.0
|
HB3
|
B:ALA362
|
3.7
|
19.7
|
1.0
|
H6
|
B:W5N501
|
4.0
|
26.3
|
1.0
|
HB3
|
B:ASP262
|
4.1
|
18.4
|
1.0
|
H26
|
B:W5N501
|
4.2
|
24.8
|
1.0
|
CB
|
B:ASP262
|
4.2
|
17.7
|
1.0
|
O
|
B:HOH788
|
4.2
|
20.3
|
1.0
|
ND1
|
B:HIS331
|
4.2
|
22.1
|
1.0
|
CG
|
B:HIS331
|
4.3
|
20.6
|
1.0
|
CG
|
B:GLU364
|
4.3
|
27.3
|
1.0
|
HB3
|
B:GLU364
|
4.3
|
24.9
|
1.0
|
H4
|
B:W5N501
|
4.4
|
26.5
|
1.0
|
CG
|
B:GLU459
|
4.4
|
16.3
|
1.0
|
HG2
|
B:GLU364
|
4.4
|
25.4
|
1.0
|
HG3
|
B:GLU459
|
4.4
|
16.8
|
1.0
|
HA2
|
B:GLY330
|
4.4
|
25.3
|
1.0
|
HB2
|
B:ASP262
|
4.6
|
18.4
|
1.0
|
HD13
|
B:ILE338
|
4.7
|
26.0
|
1.0
|
C12
|
B:W5N501
|
4.8
|
23.7
|
1.0
|
HG2
|
B:GLU459
|
4.9
|
16.8
|
1.0
|
CB
|
B:GLU364
|
4.9
|
24.3
|
1.0
|
OD2
|
B:ASP251
|
4.9
|
21.5
|
1.0
|
CA
|
B:ALA362
|
5.0
|
20.2
|
1.0
|
C5
|
B:W5N501
|
5.0
|
26.0
|
1.0
|
|
Reference:
P.Cornelius,
B.A.Mayes,
J.S.Petersen,
D.J.Turnquist,
P.J.Dufour,
A.J.Dannenberg,
J.M.Shanahan,
B.J.Carver.
Pharmacological Characterization of Sdx-7320/Evexomostat: A Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-Tumor and Anti-Metastatic Activity. Mol.Cancer Ther. 2024.
ISSN: ESSN 1538-8514
PubMed: 38530115
DOI: 10.1158/1535-7163.MCT-23-0574
Page generated: Sun Oct 6 13:30:51 2024
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