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The M2 channel is the target of a class of drugs called the adamantanes, which block the channel pore and prevent the virus from replicating. In recent decades mutations have arisen in M2 that prevent the adamantanes from binding to the channel pore, with the most prevalent of these mutations being S31N. Here we report the first crystal structure of the S31N mutant crystallized using lipidic cubic phase crystallization techniques and solved to 1.59 \u00c5 resolution. The Asn31 residues point directly into the center of the channel pore and form a hydrogen\u2010bonded network that disrupts the drug\u2010binding site. Ordered waters in the channel pore form a continuous hydrogen bonding network from Gly34 to His37.<\/jats:p>","DOI":"10.1002\/pro.2937","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T23:58:41Z","timestamp":1460764721000},"page":"1551-1554","source":"Crossref","is-referenced-by-count":40,"title":["Crystal structure of the drug\u2010resistant S31N influenza M2 proton channel"],"prefix":"10.1002","volume":"25","author":[{"given":"Jessica L.","family":"Thomaston","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry University of California San Francisco 555 Mission Bay Blvd. (S) Room 452V San Francisco California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"DeGrado","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry University of California San Francisco 555 Mission Bay Blvd. (S) Room 452V San Francisco California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905726106"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00119-10"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja400146z"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01184-08"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08722"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06528"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90730-D"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)91187-Y"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119115"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902548106"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216526110"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518493112"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811720106"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp800171m"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401997111"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.08.030"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja508461m"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.2937","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.2937","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T22:17:16Z","timestamp":1696457836000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.2937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,17]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1002\/pro.2937"],"URL":"https:\/\/doi.org\/10.1002\/pro.2937","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,17]]}}}