5I5Y
X-RAY CRYSTAL STRUCTURE AT 1.81A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH AN ARYL ACETATE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.
Summary for 5I5Y
| Entry DOI | 10.2210/pdb5i5y/pdb |
| Related | 5I5S 5I5T 5I5U 5I5V 5I5W 5I5X 5I60 |
| Descriptor | Branched-chain-amino-acid aminotransferase, mitochondrial, PYRIDOXAL-5'-PHOSPHATE, {2-[(5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carbonyl)amino]phenyl}acetic acid, ... (7 entities in total) |
| Functional Keywords | fold type iv, transferase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Isoform A: Mitochondrion. Isoform B: Cytoplasm: O15382 |
| Total number of polymer chains | 2 |
| Total formula weight | 85424.30 |
| Authors | Somers, D.O. (deposition date: 2016-02-15, release date: 2016-03-23, Last modification date: 2024-05-01) |
| Primary citation | Borthwick, J.A.,Ancellin, N.,Bertrand, S.M.,Bingham, R.P.,Carter, P.S.,Chung, C.W.,Churcher, I.,Dodic, N.,Fournier, C.,Francis, P.L.,Hobbs, A.,Jamieson, C.,Pickett, S.D.,Smith, S.E.,Somers, D.O.,Spitzfaden, C.,Suckling, C.J.,Young, R.J. Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening. J.Med.Chem., 59:2452-2467, 2016 Cited by PubMed Abstract: Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (Tm), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility. PubMed: 26938474DOI: 10.1021/acs.jmedchem.5b01607 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.81 Å) |
Structure validation
Download full validation report
