5JRH

Crystal structure of Salmonella enterica acetyl-CoA synthetase (Acs) in complex with cAMP and Coenzyme A

Summary for 5JRH

• Entry DOI: 10.2210/pdb5jrh/pdb
• Descriptor: Acetyl-coenzyme A synthetase, COENZYME A, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE, ... (6 entities in total)
• Functional Keywords: acetyl-coenzyme a synthetase, camp, amp-forming, acetyl-coenzyme a, ligase
• Biological source: Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
• Total number of polymer chains: 2
• Total formula weight: 149217.87

Authors

Shen, L.,Zhang, Y. (deposition date: 2016-05-06, release date: 2016-12-21, Last modification date: 2023-11-08)

Primary citation

Han, X.,Shen, L.,Wang, Q.,Cen, X.,Wang, J.,Wu, M.,Li, P.,Zhao, W.,Zhang, Y.,Zhao, G.
Cyclic AMP Inhibits the Activity and Promotes the Acetylation of Acetyl-CoA Synthetase through Competitive Binding to the ATP/AMP Pocket.
J. Biol. Chem., 292:1374-1384, 2017

PubMed Abstract: The high-affinity biosynthetic pathway for converting acetate to acetyl-coenzyme A (acetyl-CoA) is catalyzed by the central metabolic enzyme acetyl-coenzyme A synthetase (Acs), which is finely regulated both at the transcriptional level via cyclic AMP (cAMP)-driven trans-activation and at the post-translational level via acetylation inhibition. In this study, we discovered that cAMP directly binds to Salmonella enterica Acs (SeAcs) and inhibits its activity in a substrate-competitive manner. In addition, cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition. A crystal structure study and site-directed mutagenesis analyses confirmed that cAMP binds to the ATP/AMP pocket of SeAcs, and restrains SeAcs in an open conformation. The cAMP contact residues are well conserved from prokaryotes to eukaryotes, suggesting a general regulatory mechanism of cAMP on Acs.

PubMed: 27974467
DOI: 10.1074/jbc.M116.753640

Experimental method

X-RAY DIFFRACTION (1.644 Å)