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.

10.7554/eLife.60470 http://scihub22266oqcxt.onion/10.7554/eLife.60470 33226337!7834017!33226337     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33226337&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Elife 2020 ; 9 (ä): ä Nephropedia Template TP {{tp|p=33226337|t=2020. Differential impact of BTK active site inhibitors on the conformational state of full-length BTK |pdf=|usr=}}{{33226337}} gab.com Text Differential impact of BTK active site inhibitors on the conformational state of full-length BTK JO: Elife http://www.kidney.de/pget.php?&tw=1&pmid=33226337 #FOAvip Bruton's tyrosine kinase (BTK) is targeted in the treatment of B-cell disorders including leukemias and lymphomas. Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site. While effective at blocking the catalytic activity of BTK, consequences of drug binding on the global conformation of full-length BTK are unknown. Here, we uncover a range of conformational effects in full-length BTK induced by a panel of active site inhibitors, including large-scale shifts in the conformational equilibria of the regulatory domains. Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form. Future development of BTK inhibitors will need to consider long-range allosteric consequences of inhibitor binding, including the emerging application of these BTK inhibitors in treating COVID-19. Twit Text FOAVip Differential impact of BTK active site inhibitors on the conformational state of full-length BTK ????Elife http://www.kidney.de/pget.php?&tw=1&pmid=33226337 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33226337 #FOAvip English Wikipedia <ref>{{Cite pmid|33226337}}</ref> Differential impact of BTK active site inhibitors on the conformational state of full-length BTK #MMPMID33226337 Joseph RE; Amatya N; Fulton DB; Engen JR; Wales TE; Andreotti A Elife 2020[Nov]; 9 (ä): ä PMID33226337show ga Bruton's tyrosine kinase (BTK) is targeted in the treatment of B-cell disorders including leukemias and lymphomas. Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site. While effective at blocking the catalytic activity of BTK, consequences of drug binding on the global conformation of full-length BTK are unknown. Here, we uncover a range of conformational effects in full-length BTK induced by a panel of active site inhibitors, including large-scale shifts in the conformational equilibria of the regulatory domains. Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form. Future development of BTK inhibitors will need to consider long-range allosteric consequences of inhibitor binding, including the emerging application of these BTK inhibitors in treating COVID-19. |*Catalytic Domain[MESH] |Adenine/analogs & derivatives/chemistry/metabolism/pharmacology[MESH] |Agammaglobulinaemia Tyrosine Kinase/*antagonists & inhibitors/chemistry/genetics[MESH] |COVID-19/metabolism/prevention & control/virology[MESH] |Dasatinib/chemistry/metabolism/pharmacology[MESH] |Humans[MESH] |Leukemia, Lymphocytic, Chronic, B-Cell/genetics/prevention & control[MESH] |Models, Molecular[MESH] |Molecular Structure[MESH] |Mutation[MESH] |Piperidines/chemistry/metabolism/pharmacology[MESH] |Protein Conformation/*drug effects[MESH] |Protein Kinase Inhibitors/chemistry/metabolism/*pharmacology[MESH] |SARS-CoV-2/physiology[MESH]Differential impact of BTK active site inhibitors on the conformationa(epmc).pdf DeepDyve Pubget Overpricing