4CXR

Mycobaterium tuberculosis transaminase BioA complexed with 1-(1,3- benzothiazol-2-yl)methanamine

Replaces:  4MQO

Summary for 4CXR

• Entry DOI: 10.2210/pdb4cxr/pdb
• Related: 4CXQ 4MQP 4MQQ 4MQR
• Descriptor: ADENOSYLMETHIONINE-8-AMINO-7-OXONONANOATE AMINOTRANSFERASE, PYRIDOXAL-5'-PHOSPHATE, 1-(1,3-benzothiazol-2-yl)methanamine, ... (6 entities in total)
• Functional Keywords: transferase, transaminase, tuberculosis, plp
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 2
• Total formula weight: 97985.75

Authors

Dai, R.,Geders, T.W.,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

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: 24482078
DOI: 10.1002/CBIC.201300748

Experimental method

X-RAY DIFFRACTION (1.7 Å)