3O2G
Crystal Structure of Human gamma-butyrobetaine,2-oxoglutarate dioxygenase 1 (BBOX1)
Summary for 3O2G
| Entry DOI | 10.2210/pdb3o2g/pdb |
| Related | 3MS5 |
| Descriptor | Gamma-butyrobetaine dioxygenase, ZINC ION, N-OXALYLGLYCINE, ... (6 entities in total) |
| Functional Keywords | gamma-butyrobetaine hydroxylase, gamma-butyrobetaine, 2-oxoglutarate dioxygenase 1, oxidoreductase, structural genomics, structural genomics consortium, sgc |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 45596.40 |
| Authors | Krojer, T.,Kochan, G.,McDonough, M.A.,von Delft, F.,Leung, I.K.H.,Henry, L.,Claridge, T.D.W.,Pilka, E.,Ugochukwu, E.,Muniz, J.,Filippakopoulos, P.,Bountra, C.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Kavanagh, K.L.,Schofield, C.J.,Oppermann, U.,Structural Genomics Consortium (SGC) (deposition date: 2010-07-22, release date: 2010-09-15, Last modification date: 2024-02-21) |
| Primary citation | Leung, I.K.,Krojer, T.J.,Kochan, G.T.,Henry, L.,von Delft, F.,Claridge, T.D.,Oppermann, U.,McDonough, M.A.,Schofield, C.J. Structural and mechanistic studies on gamma-butyrobetaine hydroxylase. Chem. Biol., 17:1316-1324, 2010 Cited by PubMed Abstract: The final step in carnitine biosynthesis is catalyzed by γ-butyrobetaine (γBB) hydroxylase (BBOX), an iron/2-oxoglutarate (2OG) dependent oxygenase. BBOX is inhibited by trimethylhydrazine-propionate (THP), a clinically used compound. We report structural and mechanistic studies on BBOX and its reaction with THP. Crystallographic and sequence analyses reveal that BBOX and trimethyllysine hydroxylase form a subfamily of 2OG oxygenases that dimerize using an N-terminal domain. The crystal structure reveals the active site is enclosed and how THP competes with γBB. THP is a substrate giving formaldehyde (supporting structural links with histone demethylases), dimethylamine, malonic acid semi-aldehyde, and an unexpected product with an additional carbon-carbon bond resulting from N-demethylation coupled to oxidative rearrangement, likely via an unusual radical mechanism. The results provide a basis for development of improved BBOX inhibitors and may inspire the discovery of additional rearrangement reactions. PubMed: 21168767DOI: 10.1016/j.chembiol.2010.09.016 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.78 Å) |
Structure validation
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