Solution Structure and Acid‐Base Properties of Reduced α‐Conotoxin MI

Abstract

The reduced derivative of α‐conotoxin MI, a 14 amino acid peptide is characterized by NMR‐pH titrations and molecular dynamics simulations to determine the protonation constants of the nine basic moieties, including four cysteine thiolates, and the charge‐dependent structural properties. The peptide conformation at various protonation states was determined. The results show that the disulfide motifs in the native globular α‐conotoxin MI occur between those cysteine moieties that exhibit the most similar thiolate basicities. Since the basicity of thiolates correlates to its redox potential, this phenomenon can be explained by the higher reactivity of the two thiolates with higher basicities. The folding of the oxidized peptide is further facilitated by the loop‐like structure of the reduced form, which brings the thiolate groups into sufficient proximity. The 9 group‐specific protonation constants and the related, charge‐dependent, species‐specific peptide structures are presented.

The 3/4- and 3/6-Subfamily Variants of α-Conotoxins GI and MI Exhibit Potent Inhibitory Activity against Muscular Nicotinic Acetylcholine Receptors

“…CD spectra (Figure 3) of the GI and MI variants showed that wild-type GI and MI have a certain number of α-helices because they exhibit negative peaks at 222 and 208 nm, consistent with their NMR structures [38,39]. However, after the addition of one or two amino acids in loop 2, the α-helix content of the variants, such as GI…”