Download citation
Download citation
link to html
The X-ray crystal structure of Torpedo californica acetylcholinesterase (TcAChE) complexed with BW284C51 {CO[-­CH2CH2-pC6H4-N(CH3)2(CH2-CH=CH2)]2} is described and compared with the complexes of two other active-site gorge-spanning inhibitors, decamethonium and E2020. The inhibitor was soaked into TcAChE crystals in the trigonal space group P3121, yielding a complex which diffracted to 2.85 Å resolution. The structure was refined to an R factor of 19.0% and an Rfree of 23.4%; the final model contains the protein, inhibitor, 132 water molecules and three carbohydrate moieties. BW284C51 binds similarly to decamethonium and E2020, with its two phenyl and quaternary amino end-groups complexed to Trp84 in the catalytic site and to Trp279 in the peripheral binding site, and its central carbonyl group hydrogen bonded very weakly to Tyr121. Possible reasons for decamethonium's weaker binding are considered. The relative strength of binding of bisquaternary inhibitors to acetylcholinesterase and the effect of several mutations of the enzyme are discussed in the context of the respective X-ray structures of their complexes with the enzyme.

Supporting information

PDB reference: acetylcholinesterase–BW284C51 complex, 1e3q, r1e3qsf


Follow Acta Cryst. D
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds