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Crystal structure of protein lysine acetyltransferase Rv0998 from Mycobacterium tuberculosis
Structural highlights
FunctionPAT_MYCTU Catalyzes specifically the acetylation of the epsilon-amino group of a highly conserved lysine residue in acetyl-CoA synthetase (ACS). This acetylation results in the inactivation of ACS activity and could be important for mycobacteria to adjust to environmental changes.[1] [2] [3] Publication Abstract from PubMedProtein lysine acetylation networks can regulate central processes such as carbon metabolism and gene expression in bacteria. In Escherichia coli, cyclic AMP (cAMP) regulates protein lysine acetyltransferase (PAT) activity at the transcriptional level, but in Mycobacterium tuberculosis, fusion of a cyclic nucleotide-binding domain to a Gcn5-like PAT domain enables direct cAMP control of protein acetylation. Here we describe the allosteric activation mechanism of M. tuberculosis PAT. The crystal structures of the autoinhibited and cAMP-activated PAT reveal that cAMP binds to a cryptic site in the regulatory domain that is over 32 A from the catalytic site. An extensive conformational rearrangement relieves this autoinhibition by means of a substrate-mimicking lid that covers the protein-substrate binding surface. A steric double latch couples the domains by harnessing a classic, cAMP-mediated conformational switch. The structures suggest general features that enable the evolution of long-range communication between linked domains. Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis.,Lee HJ, Lang PT, Fortune SM, Sassetti CM, Alber T Nat Struct Mol Biol. 2012 Aug 3;19(8):811-8. doi: 10.1038/nsmb.2318. Epub 2012, Jul 8. PMID:22773105[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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