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Science 22 September 1989:
Vol. 245. no. 4924, pp. 1382 - 1385
DOI: 10.1126/science.2476850
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Articles

Science, Vol 245, Issue 4924, 1382-1385
Copyright © 1989 by American Association for the Advancement of Science

articles

Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor

R MacKinnon and C Miller

Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02254.

The inhibition by charybdotoxin of A-type potassium channels expressed in Xenopus oocytes was studied for several splicing variants of the Drosophila Shaker gene and for several site-directed mutants of this channel. Charybdotoxin blocking affinity is lowered by a factor of 3.5 upon replacing glutamate-422 with glutamine, and by a factor of about 12 upon substituting lysine in this position. Replacement of glutamate-422 by aspartate had no effect on toxin affinity. Thus, the glutamate residue at position 422 of this potassium channel is near or in the externally facing mouth of the potassium conduction pathway, and the positively charged toxin is electrostatically focused toward its blocking site by the negative potential set up by glutamate-422.


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