4BG1
Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 1-(3-Carboxypropyl)-1-methylpyrrolidin-1-ium chloride
Summary for 4BG1
| Entry DOI | 10.2210/pdb4bg1/pdb |
| Related | 4BGK 4BGM 4BHF 4BHI 4C5W |
| Descriptor | GAMMA-BUTYROBETAINE DIOXYGENASE, N-OXALYLGLYCINE, 1-(3-carboxypropyl)-1-methylpyrrolidin-1-ium, ... (6 entities in total) |
| Functional Keywords | oxidoreductase, gamma-butyrobetaine hydroxylase, gamma-bbh, gamma-butyrobetaine, 2-oxoglutarate dioxygenase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 45472.04 |
| Authors | Tars, K.,Leitans, J.,Kazaks, A. (deposition date: 2013-03-22, release date: 2014-03-12, Last modification date: 2023-12-20) |
| Primary citation | Tars, K.,Leitans, J.,Kazaks, A.,Zelencova, D.,Liepinsh, E.,Kuka, J.,Makrecka, M.,Lola, D.,Andrianovs, V.,Gustina, D.,Grinberga, S.,Liepinsh, E.,Kalvinsh, I.,Dambrova, M.,Loza, E.,Pugovics, O. Targeting Carnitine Biosynthesis: Discovery of New Inhibitors Against Gamma-Butyrobetaine Hydroxylase. J.Med.Chem., 57:2213-, 2014 Cited by PubMed Abstract: γ-Butyrobetaine hydroxylase (BBOX) catalyzes the conversion of gamma butyrobetaine (GBB) to l-carnitine, which is involved in the generation of metabolic energy from long-chain fatty acids. BBOX inhibitor 3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate (mildronate), which is an approved, clinically used cardioprotective drug, is a relatively poor BBOX inhibitor and requires high daily doses. In this paper we describe the design, synthesis, and properties of 51 compounds, which include both GBB and mildronate analogues. We have discovered novel BBOX inhibitors with improved IC50 values; the best examples are in the nanomolar range and about 2 orders of magnitude better when compared to mildronate. For six inhibitors, crystal structures in complex with BBOX have been solved to explain their activities and pave the way for further inhibitor design. PubMed: 24571165DOI: 10.1021/JM401603E PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.89 Å) |
Structure validation
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