5KEI

Mycobacterium smegmatis MbtA apo structure

Summary for 5KEI

• Entry DOI: 10.2210/pdb5kei/pdb
• Descriptor: 2,3-dihydroxybenzoate-AMP ligase (2 entities in total)
• Functional Keywords: 2, 3-dihydroxybenzoate-amp ligase, mycobactin, acetyl-coa synthetase-like, ligase
• Biological source: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
• Total number of polymer chains: 1
• Total formula weight: 59045.77

Authors

Favrot, L.,Vergnolle, O.,Blanchard, J.S. (deposition date: 2016-06-09, release date: 2016-09-14, Last modification date: 2023-09-27)

Primary citation

Vergnolle, O.,Xu, H.,Tufariello, J.M.,Favrot, L.,Malek, A.A.,Jacobs, W.R.,Blanchard, J.S.
Post-translational Acetylation of MbtA Modulates Mycobacterial Siderophore Biosynthesis.
J.Biol.Chem., 291:22315-22326, 2016

PubMed Abstract: Iron is an essential element for life, but its soluble form is scarce in the environment and is rarer in the human body. Mtb (Mycobacterium tuberculosis) produces two aryl-capped siderophores, mycobactin (MBT) and carboxymycobactin (cMBT), to chelate intracellular iron. The adenylating enzyme MbtA catalyzes the first step of mycobactin biosynthesis in two half-reactions: activation of the salicylic acid as an acyl-adenylate and ligation onto the acyl carrier protein (ACP) domain of MbtB to form covalently salicylated MbtB-ACP. We report the first apo-MbtA structure from Mycobacterium smegmatis at 2.3 Å. We demonstrate here that MbtA activity can be reversibly, post-translationally regulated by acetylation. Indeed the mycobacterial Pat (protein lysine acetyltransferase), Rv0998, specifically acetylates MbtA on lysine 546, in a cAMP-dependent manner, leading to enzyme inhibition. MbtA acetylation can be reversed by the NAD-dependent DAc (deacetyltransferase), Rv1151c. Deletion of Pat and DAc genes in Mtb revealed distinct phenotypes for strains lacking one or the other gene at low pH and limiting iron conditions. This study establishes a direct connection between the reversible acetylation system Pat/DAc and the ability of Mtb to adapt in limited iron conditions, which is critical for mycobacterial infection.

PubMed: 27566542
DOI: 10.1074/jbc.M116.744532

Experimental method

X-RAY DIFFRACTION (2.325 Å)