4MQQ: Mycobaterium Tuberculosis Transaminase Bioa Complexed With Benzo[d]thiazole-2-carbohydrazide

Citation:
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.
PDB ID: 4MQQDownload
MMDB ID: 118042
PDB Deposition Date: 2013/9/16
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4MQQ: dimeric; determined by author and by software (PISA)
Molecular Components in 4MQQ
Label Count Molecule
Proteins (2 molecules)
2
Adenosylmethionine-8-amino-7-oxononanoate Aminotransferase
Molecule annotation
Chemicals (8 molecules)
1
4
2
1
3
2
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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