Biochimica et Biophysica Acta - Proteins and Proteomics
Biochimica et Biophysica Acta - Proteins and Proteomics
5 years ago

Crystal structure of l-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis

Crystal structure of l-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis
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.

Publisher URL: www.sciencedirect.com/science

DOI: S157096391730225X

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.