Role of Aromatic Residues in the Structure-Function Relationship of α-Bungarotoxin

Yee Hsiung Chen, Jang Chyi Tai, Wan Jen Huang, Ming Zong Lai, Mien Chie Hung, Ming Derg Lai, Jen Tsi Yang

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The conformation of α-bungarotoxin and its cyanogen bromide cleaved and nitrated derivatives was studied by circular dichroism (CD). Native toxin contains no helices but some β forms and possibly β turns. Its ordered conformation is little affected when the peptide bond between Met-27 and Trp-28 is cleaved; however, the CD due to Trp-28 is abolished. The CNBr-cleaved derivative retains its immunoaffinity toward anti-toxin sera but loses its neurotoxicity toward the acetylcholine receptor. On the basis of both CD and fluorescence spectra, Trp-28 is probably stabilized by a short-range interaction with the carboxylate group of Asp-30. The ordered conformation of the toxin is also unaltered when one of the two tyrosine residues, identified as Tyr-54, is nitrated with tetranitromethane. This Tyr(N02)-54 derivative possesses both immunoaffinity and neurotoxicity. However, the toxin is denatured and loses its activities when the other tyrosine residue, Tyr-24, is also nitrated in 6 M guanidine hydrochloride, even after the denaturant is removed. Spectrophotometric titration of the toxin indicates that Tyr-54 has a normal apparent dissociation constant (pKa = 9.7) and Tyr-24 ionizes at pH above 11.2. Both tyrosine residues are in a polar environment, but Tyr-24 is not readily accessible to reagents and is stabilized by long-range interactions, probably involving Glu-41.

Original languageEnglish
Pages (from-to)2592-2600
Number of pages9
JournalBiochemistry
Volume21
Issue number11
DOIs
Publication statusPublished - 1982 May

All Science Journal Classification (ASJC) codes

  • Biochemistry

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