6add

The crystal structure of Rv2747 from Mycobacterium tuberculosis in complex with CoA and NLQ

spinqualitylabelsall models 6add, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6add is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.301Å Ligands: COA, NLQ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ARGA_MYCTU Catalyzes the conversion of L-glutamate to alpha-N-acetyl-L-glutamate. L-glutamine is a significantly better substrate compared to L-glutamate. Publication Abstract from PubMed 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 3.0A resolution respectively. The Mtb ArgA protomer was found to have a "V" cleft and a "beta" 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. Structural insights into the substrate binding mechanism of novel ArgA from Mycobacterium tuberculosis.,Das U, Singh E, Dharavath S, Subhramanyam UKT, Pal RK, Vijayan R, Menon S, Kumar S, Gourinath S, Srinivasan A Int J Biol Macromol. 2018 Dec 18. pii: S0141-8130(18)35189-4. doi:, 10.1016/j.ijbiomac.2018.12.163. PMID:30576731 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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