Manganese in PDB 6st3: Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide

All present enzymatic activity of Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide:
1.14.11.29;

The structure of Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide, PDB code: 6st3 was solved by R.Chowdhury, J.P.Holt-Martyn, C.J.Schofield, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	58.12 / 2.43
Space group	P 21 2 21
Cell size a, b, c (Å), α, β, γ (°)	72.870, 80.580, 83.920, 90.00, 90.00, 90.00
R / Rfree (%)	19.2 / 21.7

The binding sites of Manganese atom in the Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide (pdb code 6st3). This binding sites where shown within 5.0 Angstroms radius around Manganese atom.
In total 2 binding sites of Manganese where determined in the Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide, PDB code: 6st3:
Jump to Manganese binding site number: 1; 2;

Manganese binding site 1 out of 2 in the Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 1 of Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide within 5.0Å range: probe atom residue distance (Å) B Occ A:Mn603 b:26.9 occ:1.00 NE2 A:HIS374 1.9 42.0 1.0 NE2 A:HIS313 2.0 44.3 1.0 N05 A:LUW601 2.0 29.6 1.0 OD1 A:ASP315 2.1 42.1 1.0 O A:HOH717 2.1 27.3 1.0 N08 A:LUW601 2.2 31.1 1.0 CE1 A:HIS374 2.7 39.1 1.0 CE1 A:HIS313 2.8 40.2 1.0 C06 A:LUW601 2.8 30.8 1.0 HE1 A:HIS313 2.8 48.3 1.0 N07 A:LUW601 2.8 31.4 1.0 HE1 A:HIS374 2.8 46.9 1.0 C04 A:LUW601 3.0 29.3 1.0 CG A:ASP315 3.0 37.9 1.0 CD2 A:HIS374 3.0 39.1 1.0 H041 A:LUW601 3.1 35.2 1.0 CD2 A:HIS313 3.2 41.4 1.0 OD2 A:ASP315 3.3 37.6 1.0 HD2 A:HIS374 3.3 46.9 1.0 C09 A:LUW601 3.5 30.8 1.0 HD2 A:HIS313 3.5 49.7 1.0 H091 A:LUW601 3.9 37.0 1.0 ND1 A:HIS374 3.9 39.0 1.0 ND1 A:HIS313 4.0 40.4 1.0 HZ A:PHE366 4.0 41.2 1.0 O A:HOH729 4.0 40.8 1.0 CG A:HIS374 4.1 38.1 1.0 N12 A:LUW601 4.1 34.2 1.0 C11 A:LUW601 4.1 30.7 1.0 HZ2 A:TRP389 4.2 36.6 1.0 CG A:HIS313 4.2 39.9 1.0 HA A:ASP315 4.2 43.6 1.0 C03 A:LUW601 4.3 32.3 1.0 CB A:ASP315 4.4 37.0 1.0 C10 A:LUW601 4.4 30.9 1.0 HD1 A:HIS374 4.6 46.9 1.0 C13 A:LUW601 4.7 34.6 1.0 HD1 A:HIS313 4.7 48.5 1.0 CA A:ASP315 4.7 36.4 1.0 HG21 A:THR325 4.7 38.5 1.0 H A:ASP315 4.8 41.9 1.0 H111 A:LUW601 4.8 36.8 1.0 CZ A:PHE366 4.9 34.3 1.0 N A:ASP315 4.9 34.9 1.0 HB2 A:ASP315 4.9 44.4 1.0 HB3 A:ASP315 4.9 44.4 1.0 HE1 A:PHE366 5.0 39.4 1.0

Manganese binding site 2 out of 2 in the Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide


Mono view


Stereo pair view

A full contact list of Manganese with other atoms in the Mn binding site number 2 of Hif Prolyl Hydroxylase 2 (PHD2/ EGLN1) in Complex with 4-Hydroxy-N-(4- Phenoxybenzyl)-2-(1H-Pyrazol-1-Yl)Pyrimidine-5-Carboxamide within 5.0Å range: probe atom residue distance (Å) B Occ B:Mn501 b:24.8 occ:1.00 N08 B:LUW502 2.0 31.4 1.0 N05 B:LUW502 2.0 30.8 1.0 NE2 B:HIS374 2.1 32.2 1.0 NE2 B:HIS313 2.1 39.5 1.0 OD1 B:ASP315 2.1 38.4 1.0 O B:HOH614 2.3 24.9 1.0 N07 B:LUW502 2.6 30.9 1.0 C06 B:LUW502 2.7 31.6 1.0 CE1 B:HIS374 2.9 30.3 1.0 HE1 B:HIS374 2.9 36.3 1.0 CE1 B:HIS313 2.9 37.6 1.0 HE1 B:HIS313 3.0 45.1 1.0 CG B:ASP315 3.1 33.8 1.0 C04 B:LUW502 3.1 35.2 1.0 C09 B:LUW502 3.2 31.1 1.0 CD2 B:HIS374 3.2 29.6 1.0 CD2 B:HIS313 3.2 39.0 1.0 H041 B:LUW502 3.3 42.2 1.0 OD2 B:ASP315 3.3 33.7 1.0 HD2 B:HIS374 3.5 35.5 1.0 HD2 B:HIS313 3.5 46.8 1.0 H091 B:LUW502 3.6 37.4 1.0 C11 B:LUW502 3.9 30.9 1.0 N12 B:LUW502 4.0 34.6 1.0 ND1 B:HIS374 4.0 30.3 1.0 HZ2 B:TRP389 4.1 33.4 1.0 ND1 B:HIS313 4.1 38.9 1.0 O B:HOH639 4.1 40.5 1.0 HZ B:PHE366 4.1 26.1 1.0 C10 B:LUW502 4.2 32.5 1.0 CG B:HIS374 4.2 29.1 1.0 CG B:HIS313 4.3 38.5 1.0 HA B:ASP315 4.3 38.4 1.0 C03 B:LUW502 4.3 39.6 1.0 CB B:ASP315 4.5 32.7 1.0 H111 B:LUW502 4.6 37.1 1.0 C13 B:LUW502 4.7 37.2 1.0 HD1 B:HIS374 4.8 36.4 1.0 CA B:ASP315 4.8 32.0 1.0 HD1 B:HIS313 4.8 46.6 1.0 HG21 B:THR325 4.9 24.7 1.0 H B:ASP315 4.9 37.9 1.0 HB2 B:ASP315 4.9 39.2 1.0 HE1 B:PHE366 5.0 26.3 1.0 CZ B:PHE366 5.0 21.8 1.0 N B:ASP315 5.0 31.6 1.0 HB3 B:ASP315 5.0 39.2 1.0

J.Holt-Martyn, R.Chowdhury, A.Tumber, T.L.Yeh, M.I.Abboud, K.Lippl, C.Lohans, G.Langley, M.Mcdonough, C.Pugh, P.Ratcliffe, C.Schofield. Structure-Activity Relationship and Crystallographic Studies on 4-Hydroxypyrimidine Hif Prolyl Hydroxylase Domain Inhibitors. Chemmedchem 2019.
ISSN: ESSN 1860-7187
PubMed: 31751494
DOI: 10.1002/CMDC.201900557