Influence of Ionic Composition of the Medium on Acetylcholinesterase Conformation

Abstract

The recent crystallographic analysis of a dimeric glycophospholipid form of AchE from Torpedo californica (Sussman et al., 1991) provides an ideal opportunity for comparing the catalytic behaviour and recognition properties of the enzyme with its atomic structure. The globular subunit is determined to be an α/ß protein containing numerous crossover motifs of the type ß-α-ß or ß-loop-ß. The catalytic residue, Ser ₂₀₀, resides 4 A above the base of a 20 A deep cavity - or gorge - lined with numerous aromatic amino acid residues accounting for approximately 40 percents of the active center surface. A catalytic charge-relay triad comprising Ser ₂₀₀-His ₄₄₀-Glu₃₂₇ is identified. Quite surprisingly, only few net negative amino acid residues are found within the gorge: Asp ₂₈₅ and Glu ₂₇₃ at the top, Asp ₇₂ about half-way into the gorge, and G1u ₁₉₉, proximal to Ser ₂₀₀, near the base. Overall, the atomic coordinates afford a picture of the active center as that of a deep, highly aromatic cavity, rich in pi-electron density. No evidence exists for an anionic choline-binding locus situated approximately 5 A from Ser ₂₀₀.