{"id":6194,"date":"2023-02-17T07:11:06","date_gmt":"2023-02-17T07:11:06","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2017-insights-into-the-mechanism-of-membrane-pyrophosphatases-by-combining-experiment-and-computer-simulation\/"},"modified":"2023-02-17T07:11:06","modified_gmt":"2023-02-17T07:11:06","slug":"2017-insights-into-the-mechanism-of-membrane-pyrophosphatases-by-combining-experiment-and-computer-simulation","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2017-insights-into-the-mechanism-of-membrane-pyrophosphatases-by-combining-experiment-and-computer-simulation\/","title":{"rendered":"2017 &#8211; Insights into the mechanism of membrane pyrophosphatases by combining experiment and computer simulation"},"content":{"rendered":"<p>Membrane-integral pyrophosphatases (mPPases) couple the hydrolysis of pyrophosphate (PPi) to the pumping of Na<sup>+<\/sup>, H+, or both these ions across a membrane. Recently solved structures of the Na<sup>+<\/sup>-pumping\u00a0Thermotoga maritima\u00a0mPPase (TmPPase) and H+-pumping\u00a0Vigna radiata\u00a0mPPase revealed the basis of ion selectivity between these enzymes and provided evidence for the mechanisms of substrate hydrolysis and ion-pumping. Our atomistic molecular dynamics (MD) simulations of TmPPase demonstrate that loop 5\u20136 is mobile in the absence of the substrate or substrate-analogue bound to the active site, explaining the lack of electron density for this loop in resting state structures. Furthermore, creating an\u00a0apo\u00a0model of TmPPase by removing ligands from the TmPPase:IDP:Na structure in MD simulations resulted in increased dynamics in loop 5\u20136, which results in this loop moving to uncover the active site, suggesting that interactions between loop 5\u20136 and the imidodiphosphate and its associated Mg<sup>2+<\/sup>\u00a0are important for holding a loop-closed conformation. We also provide further evidence for the transport-before-hydrolysis mechanism by showing that the non-hydrolyzable substrate analogue, methylene diphosphonate, induces low levels of proton pumping by VrPPase.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36],"resource_type":[75],"application_areas":[108],"therapeutic_areas":[],"target_categories":[60],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6194","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","resource_type-publication","application_areas-transporters","target_categories-transporters"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6194","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=6194"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6194"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6194"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6194"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6194"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6194"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6194"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6194"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6194"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}