Manganese in PDB 8rgu: Arginase 2 in Complex with Inhibitor

All present enzymatic activity of Arginase 2 in Complex with Inhibitor:
3.5.3.1;

The structure of Arginase 2 in Complex with Inhibitor, PDB code: 8rgu was solved by J.Petersen, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	98.18 / 1.90
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	48.281, 134.119, 144.125, 90, 90, 90
R / Rfree (%)	20.5 / 24.6

The binding sites of Manganese atom in the Arginase 2 in Complex with Inhibitor (pdb code 8rgu). This binding sites where shown within 5.0 Angstroms radius around Manganese atom.
In total 6 binding sites of Manganese where determined in the Arginase 2 in Complex with Inhibitor, PDB code: 8rgu:
Jump to Manganese binding site number: 1; 2; 3; 4; 5; 6;

Manganese binding site 1 out of 6 in the Arginase 2 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 1 of Arginase 2 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Mn401 b:39.5 occ:1.00 OD2 A:ASP147 2.2 19.8 1.0 O A:DMS403 2.2 34.2 1.0 ND1 A:HIS120 2.2 16.3 1.0 OD2 A:ASP143 2.2 14.8 1.0 OD2 A:ASP251 2.4 17.7 1.0 C2 A:DMS403 2.4 34.7 1.0 S A:DMS403 2.8 34.8 1.0 CG A:HIS120 3.1 18.5 1.0 MN A:MN402 3.2 21.0 1.0 CG A:ASP143 3.2 15.7 1.0 CE1 A:HIS120 3.3 16.5 1.0 CG A:ASP147 3.3 19.8 1.0 CB A:HIS120 3.3 16.6 1.0 CG A:ASP251 3.4 15.4 1.0 OD1 A:ASP143 3.4 15.0 1.0 OD1 A:ASP147 3.6 20.4 1.0 CB A:ASP251 3.8 13.8 1.0 C1 A:DMS403 3.9 34.5 1.0 CD2 A:HIS120 4.2 17.7 1.0 NE2 A:HIS120 4.3 16.1 1.0 OD1 A:ASP251 4.4 13.4 1.0 NE1 A:TRP141 4.5 16.8 1.0 O A:HIS160 4.5 22.3 1.0 CB A:ASP147 4.6 20.4 1.0 CB A:ASP143 4.6 13.1 1.0 CG A:GLU296 4.6 16.2 1.0 CZ2 A:TRP141 4.7 17.3 1.0 OE2 A:GLU296 4.7 17.7 1.0 CA A:HIS120 4.8 18.0 1.0 CG2 A:VAL295 4.8 16.2 1.0 ND1 A:HIS145 4.8 17.4 1.0 OD2 A:ASP253 4.8 15.2 1.0 CB A:HIS145 4.9 16.9 1.0 CE2 A:TRP141 5.0 16.2 1.0

Manganese binding site 2 out of 6 in the Arginase 2 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 2 of Arginase 2 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:Mn402 b:21.0 occ:1.00 O A:DMS403 2.0 34.2 1.0 OD1 A:ASP143 2.1 15.0 1.0 OD2 A:ASP251 2.2 17.7 1.0 OD2 A:ASP253 2.2 15.2 1.0 ND1 A:HIS145 2.3 17.4 1.0 OD1 A:ASP253 2.3 13.2 1.0 CG A:ASP253 2.6 16.0 1.0 CG A:ASP251 3.0 15.4 1.0 CG A:ASP143 3.1 15.7 1.0 CE1 A:HIS145 3.2 16.4 1.0 MN A:MN401 3.2 39.5 1.0 S A:DMS403 3.2 34.8 1.0 C1 A:DMS403 3.3 34.5 1.0 OD2 A:ASP143 3.4 14.8 1.0 CG A:HIS145 3.4 16.4 1.0 OD1 A:ASP251 3.7 13.4 1.0 CB A:HIS145 3.7 16.9 1.0 CB A:ASP251 3.9 13.8 1.0 N A:HIS145 4.0 15.5 1.0 CB A:ASP253 4.1 14.2 1.0 C2 A:DMS403 4.2 34.7 1.0 N A:ALA144 4.2 12.3 1.0 OG1 A:THR265 4.3 28.7 1.0 NE2 A:HIS145 4.3 16.8 1.0 CB A:ASP143 4.4 13.1 1.0 CD2 A:HIS145 4.5 17.3 1.0 CA A:HIS145 4.5 17.2 1.0 CB A:ALA144 4.6 13.1 1.0 OD2 A:ASP147 4.7 19.8 1.0 O A:HOH517 4.7 19.6 1.0 CA A:ASP143 4.8 13.1 1.0 CA A:ALA144 4.8 13.8 1.0 C A:ALA144 4.8 15.0 1.0 OD1 A:ASP147 4.8 20.4 1.0 C A:ASP143 4.9 13.6 1.0

Manganese binding site 3 out of 6 in the Arginase 2 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 3 of Arginase 2 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Mn401 b:36.8 occ:1.00 OD2 B:ASP143 2.2 15.5 1.0 OD2 B:ASP147 2.2 21.8 1.0 O B:DMS403 2.3 41.5 1.0 ND1 B:HIS120 2.3 17.8 1.0 OD2 B:ASP251 2.3 19.3 1.0 C2 B:DMS403 2.6 41.4 1.0 S B:DMS403 2.9 42.7 1.0 CG B:ASP143 3.1 15.9 1.0 MN B:MN402 3.1 24.5 1.0 CG B:HIS120 3.2 20.8 1.0 CG B:ASP147 3.3 21.6 1.0 OD1 B:ASP143 3.3 15.1 1.0 CE1 B:HIS120 3.3 20.3 1.0 CG B:ASP251 3.4 15.7 1.0 CB B:HIS120 3.4 20.2 1.0 OD1 B:ASP147 3.6 23.6 1.0 CB B:ASP251 3.7 16.4 1.0 C1 B:DMS403 3.9 41.2 1.0 CD2 B:HIS120 4.4 18.4 1.0 NE1 B:TRP141 4.4 19.8 1.0 NE2 B:HIS120 4.4 21.7 1.0 OD1 B:ASP251 4.5 18.1 1.0 CB B:ASP143 4.5 13.4 1.0 O B:HIS160 4.5 21.1 1.0 CB B:ASP147 4.6 20.6 1.0 CZ2 B:TRP141 4.6 18.9 1.0 CG B:GLU296 4.7 20.1 1.0 CB B:HIS145 4.8 17.1 1.0 OE2 B:GLU296 4.9 18.9 1.0 ND1 B:HIS145 4.9 17.4 1.0 OD2 B:ASP253 4.9 21.5 1.0 CG2 B:VAL295 4.9 18.6 1.0 CE2 B:TRP141 4.9 20.0 1.0 CA B:HIS120 4.9 21.1 1.0

Manganese binding site 4 out of 6 in the Arginase 2 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 4 of Arginase 2 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ B:Mn402 b:24.5 occ:1.00 OD1 B:ASP143 2.1 15.1 1.0 OD2 B:ASP251 2.2 19.3 1.0 OD2 B:ASP253 2.3 21.5 1.0 ND1 B:HIS145 2.3 17.4 1.0 O B:DMS403 2.4 41.5 1.0 OD1 B:ASP253 2.4 17.6 1.0 CG B:ASP253 2.7 18.5 1.0 C1 B:DMS403 3.1 41.2 1.0 CG B:ASP251 3.1 15.7 1.0 CG B:ASP143 3.1 15.9 1.0 MN B:MN401 3.1 36.8 1.0 CE1 B:HIS145 3.2 19.9 1.0 S B:DMS403 3.3 42.7 1.0 CG B:HIS145 3.4 18.4 1.0 OD2 B:ASP143 3.5 15.5 1.0 CB B:HIS145 3.7 17.1 1.0 OD1 B:ASP251 3.7 18.1 1.0 CB B:ASP251 4.0 16.4 1.0 N B:HIS145 4.0 16.5 1.0 C2 B:DMS403 4.2 41.4 1.0 CB B:ASP253 4.2 16.5 1.0 N B:ALA144 4.2 14.2 1.0 OG1 B:THR265 4.3 28.4 1.0 NE2 B:HIS145 4.4 20.0 1.0 CB B:ASP143 4.4 13.4 1.0 CD2 B:HIS145 4.5 16.3 1.0 CA B:HIS145 4.5 17.8 1.0 O B:HOH515 4.6 22.2 1.0 OD2 B:ASP147 4.6 21.8 1.0 CB B:ALA144 4.7 15.4 1.0 OD1 B:ASP147 4.7 23.6 1.0 CA B:ASP143 4.8 14.2 1.0 CA B:ALA144 4.8 14.7 1.0 C B:ALA144 4.9 16.2 1.0 C B:ASP143 4.9 13.4 1.0

Manganese binding site 5 out of 6 in the Arginase 2 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 5 of Arginase 2 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ C:Mn401 b:42.5 occ:1.00 OD2 C:ASP147 2.1 18.9 1.0 O C:DMS403 2.1 39.2 1.0 ND1 C:HIS120 2.2 18.7 1.0 OD2 C:ASP143 2.3 14.2 1.0 C2 C:DMS403 2.5 40.2 1.0 OD2 C:ASP251 2.6 21.0 1.0 S C:DMS403 2.8 39.2 1.0 CG C:HIS120 3.0 19.9 1.0 MN C:MN402 3.1 23.3 1.0 CG C:ASP143 3.2 14.2 1.0 CG C:ASP147 3.2 18.2 1.0 CB C:HIS120 3.2 19.2 1.0 CE1 C:HIS120 3.3 19.6 1.0 OD1 C:ASP143 3.3 9.8 1.0 CG C:ASP251 3.6 18.1 1.0 OD1 C:ASP147 3.6 18.2 1.0 CB C:ASP251 4.0 14.6 1.0 C1 C:DMS403 4.1 38.9 1.0 CD2 C:HIS120 4.2 19.0 1.0 NE2 C:HIS120 4.3 20.5 1.0 NE1 C:TRP141 4.4 16.4 1.0 CB C:ASP147 4.4 16.0 1.0 O C:HIS160 4.4 20.8 1.0 CZ2 C:TRP141 4.6 14.5 1.0 CB C:ASP143 4.6 13.4 1.0 CB C:HIS145 4.7 15.6 1.0 OD1 C:ASP251 4.7 18.3 1.0 CA C:HIS120 4.7 19.3 1.0 ND1 C:HIS145 4.7 16.9 1.0 CG C:GLU296 4.8 18.1 1.0 OE2 C:GLU296 4.8 21.3 1.0 CE2 C:TRP141 4.9 15.1 1.0 O C:HIS145 4.9 15.2 1.0 OD2 C:ASP253 5.0 17.8 1.0

Manganese binding site 6 out of 6 in the Arginase 2 in Complex with Inhibitor


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 6 of Arginase 2 in Complex with Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ C:Mn402 b:23.3 occ:1.00 OD2 C:ASP251 2.1 21.0 1.0 O C:DMS403 2.1 39.2 1.0 OD1 C:ASP143 2.1 9.8 1.0 OD2 C:ASP253 2.4 17.8 1.0 ND1 C:HIS145 2.4 16.9 1.0 OD1 C:ASP253 2.4 17.0 1.0 CG C:ASP253 2.7 18.9 1.0 CG C:ASP251 3.1 18.1 1.0 MN C:MN401 3.1 42.5 1.0 CG C:ASP143 3.1 14.2 1.0 S C:DMS403 3.2 39.2 1.0 CE1 C:HIS145 3.2 17.0 1.0 C1 C:DMS403 3.2 38.9 1.0 OD2 C:ASP143 3.4 14.2 1.0 CG C:HIS145 3.4 17.1 1.0 OD1 C:ASP251 3.7 18.3 1.0 CB C:HIS145 3.8 15.6 1.0 C2 C:DMS403 3.9 40.2 1.0 CB C:ASP251 3.9 14.6 1.0 N C:HIS145 4.1 15.4 1.0 CB C:ASP253 4.2 15.8 1.0 N C:ALA144 4.3 13.8 1.0 NE2 C:HIS145 4.4 15.9 1.0 CB C:ASP143 4.5 13.4 1.0 OD2 C:ASP147 4.5 18.9 1.0 CD2 C:HIS145 4.5 16.2 1.0 CA C:HIS145 4.6 15.1 1.0 CB C:ALA144 4.6 14.3 1.0 O C:HOH511 4.6 21.3 1.0 CA C:ASP143 4.8 13.4 1.0 CA C:ALA144 4.8 14.5 1.0 C C:ALA144 4.9 14.3 1.0 ND1 C:HIS120 4.9 18.7 1.0 OD1 C:ASP147 4.9 18.2 1.0 C C:ASP143 5.0 13.0 1.0

S.N.Mlynarski, B.M.Aquila, S.Cantin, S.Cook, A.Doshi, M.R.V.Finlay, E.T.Gangl, T.Grebe, C.Gu, S.P.Kawatkar, J.Petersen, P.Pop-Damkov, A.G.Schuller, W.Shao, J.D.Shields, I.Simpson, S.Tavakoli, S.Tentarelli, S.Throner, H.Wang, J.Wang, D.Wu, Q.Ye. Discovery of (2 R ,4 R )-4-(( S )-2-Amino-3-Methylbutanamido)-2-(4-Boronobutyl) Pyrrolidine-2-Carboxylic Acid (AZD0011), An Actively Transported Prodrug of A Potent Arginase Inhibitor to Treat Cancer. J.Med.Chem. 2024.
ISSN: ISSN 0022-2623
PubMed: 39572889
DOI: 10.1021/ACS.JMEDCHEM.4C02309