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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.\n                  <\/jats:p>","DOI":"10.1126\/science.2476850","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T17:21:28Z","timestamp":1160068888000},"page":"1382-1385","source":"Crossref","is-referenced-by-count":263,"title":["Mutant Potassium Channels with Altered Binding of Charybdotoxin, a Pore-Blocking Peptide Inhibitor"],"prefix":"10.1126","volume":"245","author":[{"given":"Roderick","family":"MacKinnon","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, and Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Miller","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, and Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1085\/jgp.91.3.317","volume":"91","year":"1988","unstructured":"ANDERSON, C.S., CHARYBDOTOXIN BLOCK OF SINGLE CA-2+-ACTIVATED K+ CHANNELS - EFFECTS OF CHANNEL GATING, VOLTAGE, AND IONIC-STRENGTH, JOURNAL OF GENERAL PHYSIOLOGY 91: 317 (1988).","journal-title":"JOURNAL OF GENERAL PHYSIOLOGY"},{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014852"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1002\/j.1460-2075.1987.tb02665.x","volume":"6","year":"1987","unstructured":"BAUMANN, A, MOLECULAR-ORGANIZATION OF THE MATERNAL EFFECT REGION OF THE SHAKER COMPLEX OF DROSOPHILA - CHARACTERIZATION OF AN IA CHANNEL TRANSCRIPT WITH HOMOLOGY TO VERTEBRATE NA+ CHANNEL, EMBO JOURNAL 6: 3419 (1987).","journal-title":"EMBO JOURNAL"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2459775"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/306287a0","volume":"306","year":"1983","unstructured":"GETZOFF, E.D., ELECTROSTATIC RECOGNITION BETWEEN SUPEROXIDE AND COPPER, ZINC SUPEROXIDE-DISMUTASE, NATURE 306: 287 (1983).","journal-title":"NATURE"},{"key":"e_1_2_1_6_1","unstructured":"Guy H. 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