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10.1038/nchembio.2329 http://scihub22266oqcxt.onion/10.1038/nchembio.2329 C5392356!5392356!28288108     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Chem+Biol 2017 ; 13 (5): 514-21 Nephropedia Template TP {{tp|p=28288108|t=2017. Structural basis of PROTAC cooperative recognition for selective protein degradation |pdf=|usr=}}{{28288108}} gab.com Text Structural basis of PROTAC cooperative recognition for selective protein degradation JO: Nat Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=28288108 #FOAvip Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimaeras) are bifunctional molecules that recruit a target protein in proximity to an E3 ubiquitin ligase to trigger protein degradation. Structural elucidation of the key ternary ligase:PROTAC:target species and how this impacts target degradation selectivity remains elusive. We solved the crystal structure of Brd4-degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4BD2). The ligand folds into itself to allow formation of specific intermolecular interactions in the ternary complex. Isothermal titration calorimetry studies, supported by surface mutagenesis and proximity assays, are consistent with pronounced cooperative formation of ternary complexes with Brd4BD2. Structure-based-designed compound AT1 exhibits highly selective depletion of Brd4 in cells. Our results elucidate how PROTAC-induced de novo contacts dictate preferential recruitment of a target protein into a stable and cooperative complex with an E3 ligase for selective degradation. Twit Text FOAVip Structural basis of PROTAC cooperative recognition for selective protein degradation ????Nat Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=28288108 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28288108 #FOAvip English Wikipedia <ref>{{Cite pmid|28288108}}</ref> Structural basis of PROTAC cooperative recognition for selective protein degradation #MMPMID28288108 Gadd MS; Testa A; Lucas X; Chan KH; Chen W; Lamont DJ; Zengerle M; Ciulli A Nat Chem Biol 2017[May]; 13 (5): 514-21 PMID28288108show ga Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimaeras) are bifunctional molecules that recruit a target protein in proximity to an E3 ubiquitin ligase to trigger protein degradation. Structural elucidation of the key ternary ligase:PROTAC:target species and how this impacts target degradation selectivity remains elusive. We solved the crystal structure of Brd4-degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4BD2). The ligand folds into itself to allow formation of specific intermolecular interactions in the ternary complex. Isothermal titration calorimetry studies, supported by surface mutagenesis and proximity assays, are consistent with pronounced cooperative formation of ternary complexes with Brd4BD2. Structure-based-designed compound AT1 exhibits highly selective depletion of Brd4 in cells. Our results elucidate how PROTAC-induced de novo contacts dictate preferential recruitment of a target protein into a stable and cooperative complex with an E3 ligase for selective degradation. äStructural basis of PROTAC cooperative recognition for selective prote(epmc).pdf DeepDyve Pubget Overpricing