5YO2

The crystal structure of Rv2747 from Mycobacterium tuberculosis in complex with Acetyl CoA and L-Arginine

Summary for 5YO2

• Entry DOI: 10.2210/pdb5yo2/pdb
• Descriptor: Amino-acid acetyltransferase, ARGININE, ACETYL COENZYME *A (3 entities in total)
• Functional Keywords: acetyltransferase, transferase
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 2
• Total formula weight: 42525.50

Authors

Singh, E.,Tiruttani Subhramanyam, U.K.,Pal, R.K.,Srinivasan, A.,Gourinath, S.,Das, U. (deposition date: 2017-10-26, release date: 2018-11-07, Last modification date: 2024-03-27)

Primary citation

Das, U.,Singh, E.,Dharavath, S.,Tiruttani Subhramanyam, U.K.,Pal, R.K.,Vijayan, R.,Menon, S.,Kumar, S.,Gourinath, S.,Srinivasan, A.
Structural insights into the substrate binding mechanism of novel ArgA from Mycobacterium tuberculosis
Int. J. Biol. Macromol., 125:970-978, 2019

PubMed Abstract: The Mycobacterium tuberculosis (Mtb) Rv2747 gene encodes for a functional protein known as ArgA, which plays an important role in the first step of the l-arginine biosynthesis pathway. ArgA transfers the acetyl group from the acetyl-CoA to either l-glutamate or l-glutamine, which are the known substrates. Here, we present two crystal structures of ArgA: one complexed with CoA and product bound N-acetylglutamine and the other complexed with acetyl-CoA and the inhibitor l-arginine at 2.3 and 3.0 Å resolution respectively. The Mtb ArgA protomer was found to have a "V" cleft and a "β" bulge, archetypal of a classical GCN5-related N-acetyltransferase superfamily of proteins. The product bound form implies that ArgA can also acetylate l-glutamine like l-glutamate. The active site is strongly inhibited by l-arginine resulting in a closed conformation of ArgA and both l-arginine and N-acetylglutamine were found to occupy at the same active site. Together with structural analysis, molecular docking studies, microscale thermophoresis and enzyme inhibition assays, we conclude that l-glutamine, l-glutamate and l-arginine, all occupy at the same active site of ArgA. Furthermore in case of Mtb ArgA, l-arginine does not act as an allosteric inhibitor unlike other N-acetylglutamate synthase family of proteins.

PubMed: 30576731
DOI: 10.1016/j.ijbiomac.2018.12.163

Experimental method

X-RAY DIFFRACTION (2.997 Å)