5YGE

ArgA complexed with AceCoA and glutamate

5YGE の概要

• エントリーDOI: 10.2210/pdb5yge/pdb
• 分子名称: Amino-acid acetyltransferase, ACETYL COENZYME *A, GLUTAMIC ACID, ... (5 entities in total)
• 機能のキーワード: acetyltransferase, arginine biosynthesis, glutamate, acetyl coenzyme a, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41624.47

構造登録者

Yang, X.,Wu, L.,Ran, Y.,Xu, A.,Zhang, B.,Yang, X.,Zhang, R.,Rao, Z.,Li, J. (登録日: 2017-09-22, 公開日: 2017-10-11, 最終更新日: 2024-03-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.039 Å)