Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1038/nchembio.2231 http://scihub22266oqcxt.onion/10.1038/nchembio.2231 C5193369!5193369!27820802     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Chem+Biol 2017 ; 13 (1): 62-8 Nephropedia Template TP {{tp|p=27820802|t=2017. Inhibition of RAS function through targeting an allosteric regulatory site |pdf=|usr=}}{{27820802}} gab.com Text Inhibition of RAS function through targeting an allosteric regulatory site JO: Nat Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=27820802 #FOAvip RAS GTPases are important mediators of oncogenesis in humans. However, pharmacological inhibition of RAS has proved challenging. Here, we describe a functionally critical region of RAS located outside the effector lobe that can be targeted for inhibition. We developed a synthetic binding protein (monobody), termed NS1, that bound with high affinity to both GTP- and GDP-bound states of H- and K-RAS but not N-RAS. NS1 potently inhibited growth factor signaling and oncogenic H- and K-RAS-mediated signaling and transformation but did not block oncogenic N-RAS, BRAF or MEK1. NS1 bound the ?4-?6-?5 region of RAS disrupting RAS dimerization/nanoclustering, which in turn blocked CRAF:BRAF heterodimerization and activation. These results establish the importance of the ?4-?6-?5 interface in RAS-mediated signaling and define a previously unrecognized site in RAS for inhibiting RAS function. Twit Text FOAVip Inhibition of RAS function through targeting an allosteric regulatory site ????Nat Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=27820802 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27820802 #FOAvip English Wikipedia <ref>{{Cite pmid|27820802}}</ref> Inhibition of RAS function through targeting an allosteric regulatory site #MMPMID27820802 Spencer-Smith R; Koide A; Zhou Y; Eguchi RR; Sha F; Gajwani P; Santana D; Gupta A; Jacobs M; Herrero-Garcia E; Cobbert J; Lavoie H; Smith M; Rajakulendran T; Dowdell E; Okur MN; Dementieva I; Sicheri F; Therrien M; Hancock JF; Ikura M; Koide S; O?Bryan JP Nat Chem Biol 2017[Jan]; 13 (1): 62-8 PMID27820802show ga RAS GTPases are important mediators of oncogenesis in humans. However, pharmacological inhibition of RAS has proved challenging. Here, we describe a functionally critical region of RAS located outside the effector lobe that can be targeted for inhibition. We developed a synthetic binding protein (monobody), termed NS1, that bound with high affinity to both GTP- and GDP-bound states of H- and K-RAS but not N-RAS. NS1 potently inhibited growth factor signaling and oncogenic H- and K-RAS-mediated signaling and transformation but did not block oncogenic N-RAS, BRAF or MEK1. NS1 bound the ?4-?6-?5 region of RAS disrupting RAS dimerization/nanoclustering, which in turn blocked CRAF:BRAF heterodimerization and activation. These results establish the importance of the ?4-?6-?5 interface in RAS-mediated signaling and define a previously unrecognized site in RAS for inhibiting RAS function. äInhibition of RAS function through targeting an allosteric regulatory (epmc).pdf DeepDyve Pubget Overpricing