2p2b | pdb_00002p2b

Acetyl-CoA Synthetase, V386A mutation

spinqualitylabelsall models 2p2b, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2p2b is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar typhimurium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: COA, PRX Related: 1pg4, 1ry2, 1t5d, 2p20, 2p2f, 2p2j, 2p2m, 2p2q Gene: acs (Salmonella enterica subsp. enterica serovar Typhimurium) Activity: Acetate--CoA ligase, with EC number 6.2.1.1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The adenylate-forming enzymes, including acyl-CoA synthetases, the adenylation domains of non-ribosomal peptide synthetases (NRPS), and firefly luciferase, perform two half-reactions in a ping-pong mechanism. We have proposed a domain alternation mechanism for these enzymes whereby, upon completion of the initial adenylation reaction, the C-terminal domain of these enzymes undergoes a 140 degrees rotation to perform the second thioester-forming half-reaction. Structural and kinetic data of mutant enzymes support this hypothesis. We present here mutations to Salmonella enterica acetyl-CoA synthetase (Acs) and test the ability of the enzymes to catalyze the complete reaction and the adenylation half-reaction. Substitution of Lys609 with alanine results in an enzyme that is unable to catalyze the adenylate reaction, while the Gly524 to leucine substitution is unable to catalyze the complete reaction yet catalyzes the adenylation half-reaction with activity comparable to the wild-type enzyme. The positions of these two residues, which are located on the mobile C-terminal domain, strongly support the domain alternation hypothesis. We also present steady-state kinetic data of putative substrate-binding residues and demonstrate that no single residue plays a dominant role in dictating CoA binding. We have also created two mutations in the active site to alter the acyl substrate specificity. Finally, the crystallographic structures of wild-type Acs and mutants R194A, R584A, R584E, K609A, and V386A are presented to support the biochemical analysis. Biochemical and crystallographic analysis of substrate binding and conformational changes in acetyl-CoA synthetase.,Reger AS, Carney JM, Gulick AM Biochemistry. 2007 Jun 5;46(22):6536-46. Epub 2007 May 12. PMID:17497934 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetyl-CoA synthetase

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