{"id":4872,"date":"2023-02-17T07:10:24","date_gmt":"2023-02-17T07:10:24","guid":{"rendered":"http:\/\/ionchanneltargets.com\/resource_library\/nav1-5-increase-throughput-by-recording-in-unattended-mode-on-the-syncropatch-384\/"},"modified":"2023-02-17T07:10:24","modified_gmt":"2023-02-17T07:10:24","slug":"2012-distinctive-features-of-catalytic-and-transport-mechanisms-in-mammalian-sarco-endoplasmic-reticulum-ca2-atpase-serca-and-cu-atp7a-b-atpases","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2012-distinctive-features-of-catalytic-and-transport-mechanisms-in-mammalian-sarco-endoplasmic-reticulum-ca2-atpase-serca-and-cu-atp7a-b-atpases\/","title":{"rendered":"2012 &#8211; Distinctive features of catalytic and transport mechanisms in mammalian sarco-endoplasmic reticulum Ca<sup>2+<\/sup> ATPase (SERCA) and Cu+ (ATP7A\/B) ATPases"},"content":{"rendered":"<p>Ca<sup>2+<\/sup>\u00a0(sarco-endoplasmic reticulum Ca<sup>2+<\/sup>\u00a0ATPase (SERCA)) and Cu+\u00a0(ATP7A\/B) ATPases utilize ATP through formation of a phosphoenzyme intermediate (E-P) whereby phosphorylation potential affects affinity and orientation of bound cation. SERCA E-P formation is rate-limited by enzyme activation by Ca<sup>2+<\/sup>, demonstrated by the addition of ATP and Ca<sup>2+<\/sup>\u00a0to SERCA deprived of Ca<sup>2+<\/sup>\u00a0(E2) as compared with ATP to Ca<sup>2+<\/sup>-activated enzyme (E1\u00b72Ca<sup>2+<\/sup>). Activation by Ca<sup>2+<\/sup>\u00a0is slower at low pH (2H+\u00b7E2 to E1\u00b72Ca<sup>2+<\/sup>) and little sensitive to temperature-dependent activation energy. On the other hand, subsequent (forward or reverse) phosphoenzyme processing is sensitive to activation energy, which relieves conformational constraints limiting Ca<sup>2+<\/sup> translocation. A \u201cH+-gated pathway,\u201d demonstrated by experiments on pH variations, charge transfer, and Glu-309 mutation allows luminal Ca<sup>2+<\/sup>\u00a0release by H+\/Ca<sup>2+<\/sup>\u00a0exchange. As compared with SERCA, initial utilization of ATP by ATP7A\/B is much slower and highly sensitive to temperature-dependent activation energy, suggesting conformational constraints of the headpiece domains. Contrary to SERCA, ATP7B phosphoenzyme cleavage shows much lower temperature dependence than EP formation. ATP-dependent charge transfer in ATP7A and -B is observed, with no variation of net charge upon pH changes and no evidence of Cu+\/H+\u00a0exchange. As opposed to SERCA after Ca<sup>2+<\/sup>\u00a0chelation, ATP7A\/B does not undergo reverse phosphorylation with Pi after copper chelation unless a large N-metal binding extension segment is deleted. This is attributed to the inactivating interaction of the copper-deprived N-metal binding extension with the headpiece domains. We conclude that in addition to common (P-type) phosphoenzyme intermediate formation, SERCA and ATP7A\/B possess distinctive features of catalytic and transport mechanisms.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36],"resource_type":[75],"application_areas":[108],"therapeutic_areas":[],"target_categories":[60],"target_families":[344],"targets":[207],"resource_keyword":[],"class_list":["post-4872","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","resource_type-publication","application_areas-transporters","target_categories-transporters","target_families-p-type-atpases","targets-serca"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/4872","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=4872"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=4872"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=4872"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=4872"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=4872"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=4872"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=4872"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=4872"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=4872"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}