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10.1038/s41467-017-01760-5 http://scihub22266oqcxt.onion/10.1038/s41467-017-01760-5 C5700161!5700161 !29167449     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29167449 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Nat+Commun 2017 ; 8 (1 ): 1692 Nephropedia Template TP {{tp|p=29167449 |t=2017. Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes |pdf=|usr=}}{{29167449 }} gab.com Text Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29167449 #FOAvip Proteasome inhibitors benefit patients with multiple myeloma and B cell-dependent autoimmune disorders but exert toxicity from inhibition of proteasomes in other cells. Toxicity should be minimized by reversible inhibition of the immunoproteasome ?5i subunit while sparing the constitutive ?5c subunit. Here we report ?5i-selective inhibition by asparagine-ethylenediamine (AsnEDA)-based compounds and present the high-resolution cryo-EM structural analysis of the human immunoproteasome. Despite inhibiting noncompetitively, an AsnEDA inhibitor binds the active site. Hydrophobic interactions are accompanied by hydrogen bonding with ?5i and ?6 subunits. The inhibitors are far more cytotoxic for myeloma and lymphoma cell lines than for hepatocarcinoma or non-activated lymphocytes. They block human B-cell proliferation and promote apoptotic cell death selectively in antibody-secreting B cells, and to a lesser extent in activated human T cells. Reversible, ?5i-selective inhibitors may be useful for treatment of diseases involving activated or neoplastic B cells or activated T cells. Twit Text FOAVip Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29167449 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29167449 #FOAvip English Wikipedia <ref>{{Cite pmid|29167449 }}</ref> Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes #MMPMID29167449 Santos RLA ; Bai L ; Singh PK ; Murakami N ; Fan H ; Zhan W ; Zhu Y ; Jiang X ; Zhang K ; Assker JP ; Nathan CF ; Li H ; Azzi J ; Lin G Nat Commun 2017[Nov]; 8 (1 ): 1692 PMID29167449 show ga Proteasome inhibitors benefit patients with multiple myeloma and B cell-dependent autoimmune disorders but exert toxicity from inhibition of proteasomes in other cells. Toxicity should be minimized by reversible inhibition of the immunoproteasome ?5i subunit while sparing the constitutive ?5c subunit. Here we report ?5i-selective inhibition by asparagine-ethylenediamine (AsnEDA)-based compounds and present the high-resolution cryo-EM structural analysis of the human immunoproteasome. Despite inhibiting noncompetitively, an AsnEDA inhibitor binds the active site. Hydrophobic interactions are accompanied by hydrogen bonding with ?5i and ?6 subunits. The inhibitors are far more cytotoxic for myeloma and lymphoma cell lines than for hepatocarcinoma or non-activated lymphocytes. They block human B-cell proliferation and promote apoptotic cell death selectively in antibody-secreting B cells, and to a lesser extent in activated human T cells. Reversible, ?5i-selective inhibitors may be useful for treatment of diseases involving activated or neoplastic B cells or activated T cells. |Asparagine/analogs & derivatives/chemistry/metabolism [MESH] |B-Lymphocytes/drug effects/immunology/metabolism [MESH] |Binding Sites [MESH] |Cell Line, Tumor [MESH] |Cryoelectron Microscopy [MESH] |Humans [MESH] |Lymphocyte Activation/drug effects/immunology [MESH] |Lymphocytes/*drug effects/*immunology/metabolism [MESH] |Models, Molecular [MESH] |Proteasome Endopeptidase Complex/*chemistry/*immunology/metabolism [MESH] |Proteasome Inhibitors/*chemistry/metabolism [MESH] |Protein Subunits [MESH] |Static Electricity [MESH]Structure of human immunoproteasome with a reversible and noncompetiti(epmc).pdf DeepDyve Pubget Overpricing