5t02

Structural characterisation of mutant Asp39Ala of thioesterase (NmACH) from Neisseria meningitidis

spinqualitylabelsall models 5t02, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5t02 is a 6 chain structure with sequence from Neisseria meningitidis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: CL, COA, GDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0Y5D4F5_NEIME Publication Abstract from PubMed Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. While many of these enzyme families are well characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis. Structural analysis with X-ray crystallographic diffraction data to 2.0 A revealed that each protein subunit harbors a hot dog fold and that the TE6 enzyme forms a hexamer with D3 symmetry. An assessment of thioesterase activity against a range of acyl-CoA substrates revealed greatest activity against acetyl-CoA, and structure-guided mutagenesis of putative active site residues identified Asn-24 and Asp-39 as being essential for activity. Our structural analysis revealed that six GDP nucleotides bound the enzyme in close proximity to an intersubunit disulfide bond interactions that covalently link thioesterase domains in a double hot dog dimer. Structure-guided mutagenesis of residues within the GDP-binding pocket identified Arg-93 as playing a key role in the nucleotide interaction and revealed that GDP is required for activity. All mutations were confirmed to be specific and not to have resulted from structural perturbations by X-ray crystallography. This is the first report of a bacterial GDP-regulated thioesterase and of covalent linkage of thioesterase domains through a disulfide bond, revealing structural similarities with ADP regulation in the human ACOT12 thioesterase. Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase.,Khandokar YB, Srivastava P, Cowieson N, Sarker S, Aragao D, Das S, Smith KM, Raidal SR, Forwood JK J Biol Chem. 2017 Oct 2. pii: jbc.M117.800227. doi: 10.1074/jbc.M117.800227. PMID:28972175 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioesterase 3D structures

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