4AVC

Crystal structure of protein lysine acetyltransferase Rv0998 in complex with acetyl CoA and cAMP

Summary for 4AVC

• Entry DOI: 10.2210/pdb4avc/pdb
• Related: 4AVA 4AVB
• Descriptor: LYSINE ACETYLTRANSFERASE, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE, ACETYL COENZYME *A, ... (6 entities in total)
• Functional Keywords: transferase, acetyltransferase, allosteric regulation, domain coupling
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 2
• Total formula weight: 75106.90

Authors

Lee, H.J.,Lang, P.T.,Fortune, S.M.,Sassetti, C.M.,Alber, T. (deposition date: 2012-05-24, release date: 2012-07-11, Last modification date: 2024-11-13)

Primary citation

Lee, H.J.,Lang, P.T.,Fortune, S.M.,Sassetti, C.M.,Alber, T.
Cyclic AMP Regulation of Protein Lysine Acetylation in Mycobacterium Tuberculosis.
Nat.Struct.Mol.Biol., 19:811-, 2012

PubMed 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 autoinhibited and cAMP-activated PAT reveal that cAMP binds to a cryptic site in the regulatory domain that is over 32 Å 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.

PubMed: 22773105
DOI: 10.1038/NSMB.2318

Experimental method

X-RAY DIFFRACTION (2.806 Å)