Cyclic AMP Regulation of Protein Lysine Acetylation in Mycobacterium Tuberculosis

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Cyclic AMP Regulation of Protein Lysine Acetylation in Mycobacterium Tuberculosis

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Title: Cyclic AMP Regulation of Protein Lysine Acetylation in Mycobacterium Tuberculosis
Author: Lee, Ho Jun; Lang, P. Therese; Fortune, Sarah Merritt; Sassetti, Christopher M.; Alber, Tom

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Citation: Lee, Ho Jun, P. Therese Lang, Sarah M. Fortune, Christopher M. Sassetti, and Tom Alber. 2012. Cyclic AMP regulation of protein lysine acetylation in mycobacterium tuberculosis. Nature Structural and Molecular Biology 19(8): 811-8.
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Abstract: Protein 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 auto-inhibited and cAMP-activated PAT reveal that cAMP binds to a cryptic site in the regulatory domain over 32 Å from the catalytic site. An extensive conformational rearrangement relieves auto-inhibition by 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.
Published Version: doi:10.1038/nsmb.2318
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414669/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11379655
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