{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T05:43:56Z","timestamp":1762839836497,"version":"build-2065373602"},"reference-count":71,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871027","82404583"],"award-info":[{"award-number":["81871027","82404583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V010344\/1","BB\/R02104X\/1"],"award-info":[{"award-number":["BB\/V010344\/1","BB\/R02104X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","award":["236Z7723G"],"award-info":[{"award-number":["236Z7723G"]}],"id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002338","name":"Ministry of Education of the People's Republic of China","doi-asserted-by":"publisher","award":["NV20230001"],"award-info":[{"award-number":["NV20230001"]}],"id":[{"id":"10.13039\/501100002338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>KCNQ1\u20105 (Kv7.1\u20137.5) are members of a family of voltage\u2010gated potassium channels with prominent function in the nervous and cardiovascular systems and in epithelia. KCNQ channels are activated by intracellular free zinc, but the molecular mechanism of this effect is poorly understood and zinc binding sites within KCNQ channels are elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We used patch\u2010clamp electrophysiology, site\u2010directed mutagenesis and computational biology to investigate the action of zinc on\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/ObjectDisplayForward?objectId=560\">KCNQ1<\/jats:ext-link>\n                      and its complexes with KCNE1 or KCNE3 auxiliary subunits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Zinc ionophores,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=2597\">zinc pyrithione<\/jats:ext-link>\n                      (ZnPy) and pyrrolidinedithiocarbamate (PDTC), potently activated homotetrameric KCNQ1 channels. In contrast, heteromeric KCNQ1\/KCNE1 and KCNQ1\/KCNE3 channels were partially inhibited by ZnPy. Focussing on this difference, we identified a putative zinc coordination site in close proximity to the KCNQ1\u2010KCNE interface and a binding site for the KCNQ channel cofactor,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=2387\">phosphatidylinositol 4,5\u2010bisphosphate<\/jats:ext-link>\n                      (PIP\n                      <jats:sub>2<\/jats:sub>\n                      ). The zinc coordination site in KCNQ1 contains histidines H126 and H240, and glutamic acid E170. Additional aspartic acid D242 acts as an effector site in coupling zinc binding with channel activation. The site is partially conserved with other KCNQ subunits, although the role of D242 appears to be unique for KCNQ1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Our findings reveal a new structural modality for ligand\u2010induced activation of an important potassium channel, which can be harnessed for development of KCNQ\u2010targeting pharmaceutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70177","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T08:03:44Z","timestamp":1755677024000},"page":"6081-6099","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elucidation of the zinc binding site in KCNQ channels"],"prefix":"10.1111","volume":"182","author":[{"given":"Shuo","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology Hebei Medical University  Shijiazhuang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhe","family":"Yang","sequence":"additional","affiliation":[{"name":"CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co, Ltd  Shijiazhuang Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Hebei Medical University  Shijiazhuang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixue","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Hebei Medical University  Shijiazhuang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical and 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