5jrh

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

spinqualitylabelsall models 5jrh, resolution 1.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jrh is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.644Å Ligands: BU3, CMP, COA, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACSA_SALTY Catalyzes the conversion of acetate into acetyl-CoA (AcCoA), an essential intermediate at the junction of anabolic and catabolic pathways. Acs undergoes a two-step reaction. In the first half reaction, Acs combines acetate with ATP to form acetyl-adenylate (AcAMP) intermediate. In the second half reaction, it can then transfer the acetyl group from AcAMP to the sulfhydryl group of CoA, forming the product AcCoA. Enables the cell to use acetate during aerobic growth to generate energy via the TCA cycle, and biosynthetic compounds via the glyoxylate shunt. Acetylates CheY, the response regulator involved in flagellar movement and chemotaxis (By similarity). Publication Abstract from PubMed 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. Cyclic AMP Inhibits the Activity and Promotes the Acetylation of Acetyl-CoA Synthetase through Competitive Binding to the ATP/AMP Pocket.,Han X, Shen L, Wang Q, Cen X, Wang J, Wu M, Li P, Zhao W, Zhang Y, Zhao G J Biol Chem. 2017 Jan 27;292(4):1374-1384. doi: 10.1074/jbc.M116.753640. Epub, 2016 Dec 14. PMID:27974467 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetyl-CoA synthetase 3D structures

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