9BR7
Crystal structure of human succinyl-CoA:glutarate-CoA transferase (SUGCT) in complex with Losartan carboxylic acid
This is a non-PDB format compatible entry.
Summary for 9BR7
| Entry DOI | 10.2210/pdb9br7/pdb |
| Descriptor | Succinate--hydroxymethylglutarate CoA-transferase, losartan carboxylic acid, AMMONIUM ION, ... (5 entities in total) |
| Functional Keywords | sugct, succinyl-coa, glutarate, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 181069.97 |
| Authors | |
| Primary citation | Wu, R.,Khamrui, S.,Dodatko, T.,Leandro, J.,Sabovic, A.,Violante, S.,Cross, J.R.,Marsan, E.,Kumar, K.,DeVita, R.J.,Lazarus, M.B.,Houten, S.M. Characterization, Structure, and Inhibition of the Human Succinyl-CoA:glutarate-CoA Transferase, a Putative Genetic Modifier of Glutaric Aciduria Type 1. Acs Chem.Biol., 19:1544-1553, 2024 Cited by PubMed Abstract: Glutaric Aciduria Type 1 (GA1) is a serious inborn error of metabolism with no pharmacological treatments. A novel strategy to treat this disease is to divert the toxic biochemical intermediates to less toxic or nontoxic metabolites. Here, we report a putative novel target, succinyl-CoA:glutarate-CoA transferase (SUGCT), which we hypothesize suppresses the GA1 metabolic phenotype through decreasing glutaryl-CoA and the derived 3-hydroxyglutaric acid. SUGCT is a type III CoA transferase that uses succinyl-CoA and glutaric acid as substrates. We report the structure of SUGCT, develop enzyme- and cell-based assays, and identify valsartan and losartan carboxylic acid as inhibitors of the enzyme in a high-throughput screen of FDA-approved compounds. The cocrystal structure of SUGCT with losartan carboxylic acid revealed a novel pocket in the active site and further validated the high-throughput screening approach. These results may form the basis for the future development of new pharmacological intervention to treat GA1. PubMed: 38915184DOI: 10.1021/acschembio.4c00204 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.08 Å) |
Structure validation
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