This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4mqp

From Proteopedia

Jump to: navigation, search

Mycobaterium tuberculosis transaminase BioA complexed with 2-hydrazinylbenzo[d]thiazole

Structural highlights

4mqp is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.83Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BIOA_MYCTU Catalyzes the reversible transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only animotransferase known to utilize SAM as an amino donor. Can also use sinefungin as substrate.^[1]

Publication Abstract from PubMed

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.

Inhibition of Mycobacterium tuberculosis Transaminase BioA by Aryl Hydrazines and Hydrazides.,Dai R, Wilson DJ, Geders TW, Aldrich CC, Finzel BC Chembiochem. 2014 Mar 3;15(4):575-86. doi: 10.1002/cbic.201300748. Epub 2014 Jan , 31. PMID:24482078^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mann S, Ploux O. 7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic target. Characterization and inhibition studies. FEBS J. 2006 Oct;273(20):4778-89. Epub 2006 Sep 19. PMID:16984394 doi:10.1111/j.1742-4658.2006.05479.x
↑ Dai R, Wilson DJ, Geders TW, Aldrich CC, Finzel BC. Inhibition of Mycobacterium tuberculosis Transaminase BioA by Aryl Hydrazines and Hydrazides. Chembiochem. 2014 Mar 3;15(4):575-86. doi: 10.1002/cbic.201300748. Epub 2014 Jan , 31. PMID:24482078 doi:http://dx.doi.org/10.1002/cbic.201300748