4NHY
Crystal structure of human OGFOD1, 2-oxoglutarate and iron-dependent oxygenase domain containing 1, in complex with pyridine-2,4-dicarboxylic acid (2,4-PDCA)
Summary for 4NHY
| Entry DOI | 10.2210/pdb4nhy/pdb |
| Related | 4NHL 4NHM 4NHN 4NHX |
| Descriptor | 2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1, MANGANESE (II) ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | jelly-roll fold, translation, ribosome, double-stranded beta helix, oxygen sensing, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 263162.18 |
| Authors | Horita, S.,McDonough, M.A.,Schofield, C.J. (deposition date: 2013-11-05, release date: 2014-11-19, Last modification date: 2023-09-20) |
| Primary citation | Horita, S.,Scotti, J.S.,Thinnes, C.,Mottaghi-Taromsari, Y.S.,Thalhammer, A.,Ge, W.,Aik, W.,Loenarz, C.,Schofield, C.J.,McDonough, M.A. Structure of the Ribosomal Oxygenase OGFOD1 Provides Insights into the Regio- and Stereoselectivity of Prolyl Hydroxylases. Structure, 23:639-652, 2015 Cited by PubMed Abstract: Post-translational ribosomal protein hydroxylation is catalyzed by 2-oxoglutarate (2OG) and ferrous iron dependent oxygenases, and occurs in prokaryotes and eukaryotes. OGFOD1 catalyzes trans-3 prolyl hydroxylation at Pro62 of the small ribosomal subunit protein uS12 (RPS23) and is conserved from yeasts to humans. We describe crystal structures of the human uS12 prolyl 3-hydroxylase (OGFOD1) and its homolog from Saccharomyces cerevisiae (Tpa1p): OGFOD1 in complex with the broad-spectrum 2OG oxygenase inhibitors; N-oxalylglycine (NOG) and pyridine-2,4-dicarboxylate (2,4-PDCA) to 2.1 and 2.6 Å resolution, respectively; and Tpa1p in complex with NOG, 2,4-PDCA, and 1-chloro-4-hydroxyisoquinoline-3-carbonylglycine (a more selective prolyl hydroxylase inhibitor) to 2.8, 1.9, and 1.9 Å resolution, respectively. Comparison of uS12 hydroxylase structures with those of other prolyl hydroxylases, including the human hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs), reveals differences between the prolyl 3- and prolyl 4-hydroxylase active sites, which can be exploited for developing selective inhibitors of the different subfamilies. PubMed: 25728928DOI: 10.1016/j.str.2015.01.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.603 Å) |
Structure validation
Download full validation report
