Felder_2002_Acta.Crystallogr.D.Biol.Crystallogr_58_1765

Reference

Title : Structure of a complex of the potent and specific inhibitor BW284C51 with Torpedo californica acetylcholinesterase - Felder_2002_Acta.Crystallogr.D.Biol.Crystallogr_58_1765
Author(s) : Felder CE , Harel M , Silman I , Sussman JL
Ref : Acta Crystallographica D Biol Crystallogr , 58 :1765 , 2002
Abstract :

The X-ray crystal structure of Torpedo californica acetylcholinesterase (TcAChE) complexed with BW284C51 [CO[-CH(2)CH(2)-pC(6)H(4)-N(CH(3))(2)(CH(2)-CH=CH(2))](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 P3(1)21, yielding a complex which diffracted to 2.85 A resolution. The structure was refined to an R factor of 19.0% and an R(free) 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.

PubMedSearch : Felder_2002_Acta.Crystallogr.D.Biol.Crystallogr_58_1765
PubMedID: 12351819
Gene_locus related to this paper: torca-ACHE

Related information

Inhibitor BW284C51
Gene_locus BW284C51    torca-ACHE
Structure BW284C51    torca-ACHE    1E3Q

Citations formats

Felder CE, Harel M, Silman I, Sussman JL (2002)
Structure of a complex of the potent and specific inhibitor BW284C51 with Torpedo californica acetylcholinesterase
Acta Crystallographica D Biol Crystallogr 58 :1765

Felder CE, Harel M, Silman I, Sussman JL (2002)
Acta Crystallographica D Biol Crystallogr 58 :1765