6wuv

Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by GA

spinqualitylabelsall models 6wuv, resolution 2.63Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.63Å Ligands: ELT, FUC, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The recent use of organophosphate nerve agents in Syria, Malaysia, Russia, and the United Kingdom has reinforced the potential threat of their intentional release. These agents act through their ability to inhibit human acetylcholinesterase (hAChE; E.C. 3.1.1.7), an enzyme vital for survival. The toxicity of hAChE inhibition via G-series nerve agents has been demonstrated to vary widely depending on the G-agent used. To gain insight into this issue, the structures of hAChE inhibited by tabun, sarin, cyclosarin, soman, and GP were obtained along with the inhibition kinetics for these agents. Through this information, the role of hAChE active site plasticity in agent selectivity is revealed. With reports indicating that the efficacy of reactivators can vary based on the nerve agent inhibiting hAChE, human recombinatorially expressed hAChE was utilized to define these variations for HI-6 among various G-agents. To identify the structural underpinnings of this phenomenon, the structures of tabun, sarin, and soman-inhibited hAChE in complex with HI-6 were determined. This revealed how the presence of G-agent adducts impacts reactivator access and placement within the active site. These insights will contribute toward a path of next-generation reactivators and an improved understanding of the innate issues with the current reactivators. Structural and Biochemical Insights into the Inhibition of Human Acetylcholinesterase by G-Series Nerve Agents and Subsequent Reactivation by HI-6.,McGuire JR, Bester SM, Guelta MA, Cheung J, Langley C, Winemiller MD, Bae SY, Funk V, Myslinski JM, Pegan SD, Height JJ Chem Res Toxicol. 2021 Feb 4. doi: 10.1021/acs.chemrestox.0c00406. PMID:33538594 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

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