Summary for 4CXQ
| Entry DOI | 10.2210/pdb4cxq/pdb |
| Related | 4CXR 4MQP 4MQQ 4MQR |
| Descriptor | ADENOSYLMETHIONINE-8-AMINO-7-OXONONANOATE AMINOTRANSFERASE, PYRIDOXAL-5'-PHOSPHATE, 7-KETO-8-AMINOPELARGONIC ACID, ... (6 entities in total) |
| Functional Keywords | transferase, transaminase, tuberculosis |
| Biological source | MYCOBACTERIUM TUBERCULOSIS |
| Total number of polymer chains | 2 |
| Total formula weight | 98340.24 |
| Authors | Dai, R.,Wilson, D.J.,Geders, T.W.,Aldrich, C.C.,Finzel, B.C. (deposition date: 2014-04-08, release date: 2014-04-23, Last modification date: 2023-12-20) |
| Primary citation | Dai, R.,Wilson, D.J.,Geders, T.W.,Aldrich, C.C.,Finzel, B.C. Inhibition of Mycobacterium Tuberculosis Transaminase Bioa by Aryl Hydrazines and Hydrazides. Chembiochem, 15:575-, 2014 Cited by PubMed Abstract: 7,8-Diaminopelargonic acid synthase (BioA) of Mycobacterium tuberculosis is a recently validated target for therapeutic intervention in the treatment of tuberculosis (TB). Using biophysical fragment screening and structural characterization of compounds, we have identified a potent aryl hydrazine inhibitor of BioA that reversibly modifies the pyridoxal-5'-phosphate (PLP) cofactor, forming a stable quinonoid. Analogous hydrazides also form covalent adducts that can be observed crystallographically but are incapable of inactivating the enzyme. In the X-ray crystal structures, small molecules induce unexpected conformational remodeling in the substrate binding site. We compared these conformational changes to those induced upon binding of the substrate (7-keto-8-aminopelargonic acid), and characterized the inhibition kinetics and the X-ray crystal structures of BioA with the hydrazine compound and analogues to unveil the mechanism of this reversible covalent modification. PubMed: 24482078DOI: 10.1002/CBIC.201300748 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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