6ur1

Crystal structure of ChoE S38A mutant in complex with acetate and acetylthiocholine

spinqualitylabelsall models 6ur1, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ur1 is a 2 chain structure with sequence from Pseae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, AT3, GOL Related: 6uqv Gene: choE, PA4921 (PSEAE) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Mammalian acetylcholinesterase (AChE) is well studied, being important in both cholinergic brain synapses and the peripheral nervous systems and also a key drug target for many diseases. In contrast, little is known about the structures and molecular mechanism of prokaryotic acetylcholinesterases. We report here the structural and biochemical characterization of ChoE, a putative bacterial acetylcholinesterase from Pseudomonas aeruginosa. Analysis of wild-type (WT) and mutant strains indicated that ChoE is indispensable for P. aeruginosa growth with acetylcholine as the sole carbon and nitrogen source. The crystal structure of ChoE at 1.35 A resolution revealed that this enzyme adopts a typical fold of the SGNH hydrolase family. Although ChoE and eukaryotic AChEs catalyze the same reaction, their overall structures bear no similarities constituting an interesting example of convergent evolution. Among Ser-38, Asp-285, and His-288 of the catalytic triad residues, only Asp-285 was not essential for ChoE activity. Combined with kinetic analyses of WT and mutant proteins, multiple crystal structures of ChoE complexed with substrates, products, or reaction intermediate revealed the structural determinants for substrate recognition, snapshots of the various catalytic steps, and the molecular basis of substrate inhibition at high substrate concentrations. Our results indicate that substrate inhibition in ChoE is due to acetate release being blocked by the binding of a substrate molecule in a nonproductive mode. Owing to the distinct overall folds and significant differences of the active site between ChoE and eukaryotic AChEs, these structures will serve as a prototype for other prokaryotic acetylcholinesterases. Structural insights into the putative bacterial acetylcholinesterase ChoE and its substrate inhibition mechanism.,Pham VD, To TA, Gagne-Thivierge C, Couture M, Lague P, Yao D, Picard ME, Lortie LA, Attere SA, Zhu X, Levesque RC, Charette SJ, Shi R J Biol Chem. 2020 May 5. pii: RA119.011809. doi: 10.1074/jbc.RA119.011809. PMID:32371400 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

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