Matches in SemOpenAlex for { <https://semopenalex.org/work/W2993277592> ?p ?o ?g. }
- W2993277592 abstract "ABSTRACT The trinuclear ruthenium amine Ruthenium Red (RuR) inhibits diverse ion channels including K 2P potassium channels, TRPs, the mitochondrial calcium uniporter, CALHMs, ryanodine receptors, and Piezos. Despite this extraordinary array, there is very limited information for how RuR engages its targets. Here, using X-ray crystallographic and electrophysiological studies of an RuR-sensitive K 2P , K 2P 2.1 (TREK-1) I110D, we show that RuR acts by binding an acidic residue pair comprising the ‘Keystone inhibitor site’ under the K 2P CAP domain archway above the channel pore. We further establish that Ru360, a dinuclear ruthenium amine not known to affect K 2P s, inhibits RuR-sensitive K 2P s using the same mechanism. Structural knowledge enabled a generalizable RuR ‘super-responder’ design strategy for creating K 2P s having nanomolar sensitivity. Together, the data define a ‘finger in the dam’ inhibition mechanism acting at a novel K 2P inhibitor binding site. These findings highlight the polysite nature of K 2P pharmacology and provide a new framework for K 2P inhibitor development." @default.
- W2993277592 created "2019-12-13" @default.
- W2993277592 creator A5005678327 @default.
- W2993277592 creator A5045437602 @default.
- W2993277592 creator A5062700021 @default.
- W2993277592 date "2019-12-04" @default.
- W2993277592 modified "2023-09-30" @default.
- W2993277592 title "Polynuclear ruthenium amines inhibit K2P channels via a ‘finger in the dam’ mechanism" @default.
- W2993277592 cites W1495409864 @default.
- W2993277592 cites W150246076 @default.
- W2993277592 cites W1511198581 @default.
- W2993277592 cites W1545384325 @default.
- W2993277592 cites W1772956064 @default.
- W2993277592 cites W1826631511 @default.
- W2993277592 cites W1967676040 @default.
- W2993277592 cites W1967930702 @default.
- W2993277592 cites W1968077572 @default.
- W2993277592 cites W1974988689 @default.
- W2993277592 cites W1977002226 @default.
- W2993277592 cites W1980779109 @default.
- W2993277592 cites W1986213783 @default.
- W2993277592 cites W1989736892 @default.
- W2993277592 cites W1997913073 @default.
- W2993277592 cites W2006922182 @default.
- W2993277592 cites W2010572143 @default.
- W2993277592 cites W2011414076 @default.
- W2993277592 cites W2022262895 @default.
- W2993277592 cites W2029668693 @default.
- W2993277592 cites W2032443344 @default.
- W2993277592 cites W2039263971 @default.
- W2993277592 cites W2041345208 @default.
- W2993277592 cites W2069805384 @default.
- W2993277592 cites W2076413516 @default.
- W2993277592 cites W2079480529 @default.
- W2993277592 cites W2081912151 @default.
- W2993277592 cites W2084681734 @default.
- W2993277592 cites W2085554856 @default.
- W2993277592 cites W2087708225 @default.
- W2993277592 cites W2090858893 @default.
- W2993277592 cites W2092581425 @default.
- W2993277592 cites W2096104904 @default.
- W2993277592 cites W2102228853 @default.
- W2993277592 cites W2110808180 @default.
- W2993277592 cites W2111784324 @default.
- W2993277592 cites W2118622904 @default.
- W2993277592 cites W2120229762 @default.
- W2993277592 cites W2122951173 @default.
- W2993277592 cites W2123384023 @default.
- W2993277592 cites W2129809239 @default.
- W2993277592 cites W2131597783 @default.
- W2993277592 cites W2139844024 @default.
- W2993277592 cites W2144081223 @default.
- W2993277592 cites W2148011337 @default.
- W2993277592 cites W2155881793 @default.
- W2993277592 cites W2162746575 @default.
- W2993277592 cites W2166599924 @default.
- W2993277592 cites W2168174140 @default.
- W2993277592 cites W2170711116 @default.
- W2993277592 cites W2180229411 @default.
- W2993277592 cites W2283447233 @default.
- W2993277592 cites W2286255985 @default.
- W2993277592 cites W2337576024 @default.
- W2993277592 cites W2340955996 @default.
- W2993277592 cites W2343726927 @default.
- W2993277592 cites W2568125552 @default.
- W2993277592 cites W2593710600 @default.
- W2993277592 cites W2615430757 @default.
- W2993277592 cites W2724716579 @default.
- W2993277592 cites W2776223742 @default.
- W2993277592 cites W2785150634 @default.
- W2993277592 cites W2794369591 @default.
- W2993277592 cites W2886883754 @default.
- W2993277592 cites W2889224480 @default.
- W2993277592 cites W2889864310 @default.
- W2993277592 cites W2901787904 @default.
- W2993277592 cites W2904553519 @default.
- W2993277592 cites W2916379543 @default.
- W2993277592 cites W2940789172 @default.
- W2993277592 cites W2946037708 @default.
- W2993277592 cites W2959781137 @default.
- W2993277592 cites W2977241603 @default.
- W2993277592 cites W2978230380 @default.
- W2993277592 cites W2980975640 @default.
- W2993277592 cites W2988463622 @default.
- W2993277592 cites W2990548291 @default.
- W2993277592 cites W4211057422 @default.
- W2993277592 cites W4248872320 @default.
- W2993277592 doi "https://doi.org/10.1101/863837" @default.
- W2993277592 hasPublicationYear "2019" @default.
- W2993277592 type Work @default.
- W2993277592 sameAs 2993277592 @default.
- W2993277592 citedByCount "0" @default.
- W2993277592 crossrefType "posted-content" @default.
- W2993277592 hasAuthorship W2993277592A5005678327 @default.
- W2993277592 hasAuthorship W2993277592A5045437602 @default.
- W2993277592 hasAuthorship W2993277592A5062700021 @default.
- W2993277592 hasBestOaLocation W29932775921 @default.
- W2993277592 hasConcept C113217602 @default.
- W2993277592 hasConcept C12554922 @default.
- W2993277592 hasConcept C161790260 @default.