5YGE

ArgA complexed with AceCoA and glutamate

Summary for 5YGE

• Entry DOI: 10.2210/pdb5yge/pdb
• Descriptor: Amino-acid acetyltransferase, ACETYL COENZYME *A, GLUTAMIC ACID, ... (5 entities in total)
• Functional Keywords: acetyltransferase, arginine biosynthesis, glutamate, acetyl coenzyme a, transferase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 41624.47

Authors

Yang, X.,Wu, L.,Ran, Y.,Xu, A.,Zhang, B.,Yang, X.,Zhang, R.,Rao, Z.,Li, J. (deposition date: 2017-09-22, release date: 2017-10-11, Last modification date: 2024-03-27)

Primary citation

Yang, X.,Wu, L.,Ran, Y.,Xu, A.,Zhang, B.,Yang, X.,Zhang, R.,Rao, Z.,Li, J.
Crystal structure of l-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis
Biochim. Biophys. Acta, 1865:1800-1807, 2017

PubMed Abstract: l-arginine is used as a source of both carbon and nitrogen in Mycobacterium tuberculosis (Mtb) and its biosynthesis is essential for the pathogen's survival. MtbArgA (Rv2747) catalyzes the initial step in l-arginine biosynthesis by transferring an acetyl group from acetyl coenzyme A (AcCoA) to l-glutamate. MtbArgA is a class III N-acetylglutamate synthase (NAGS) with no structural information. Here, we solved the crystal structure of MtbArgA complexed with AcCoA and l-glutamate. The overall structure adopts a classic fold of the GCN5-related N-acetyltransferase (GNAT) family, characterized by a "V"-shaped cleft and β-bulge, but uses distinct residues for the binding and reaction of AcCoA. In particular, its activity depends on dimerization to form a deep, vast pocket for l-glutamate binding. Interestingly, in the structure, l-glutamate binds at a site far away from AcCoA, implying a mechanism of separate capture and catalysis. Additionally, based on a docking model of l-glutamate at the catalytic site, a one-step sequential mechanism was proposed for enzymatic catalysis. Important sites for substrate binding and catalysis were also evaluated by site-directed mutagenesis study and activity analysis. The unique features of the MtbArgA structure will provide useful insights for inhibitor design and anti-tuberculosis drug discovery.

PubMed: 28943401
DOI: 10.1016/j.bbapap.2017.09.009

Experimental method

X-RAY DIFFRACTION (2.039 Å)