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10.7554/eLife.63586 http://scihub22266oqcxt.onion/10.7554/eLife.63586 33570492!7972453!33570492     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       Elife 2021 ; 10 (ä): ä Nephropedia Template TP {{tp|p=33570492|t=2021. The allosteric modulation of complement C5 by knob domain peptides |pdf=|usr=}}{{33570492}} gab.com Text The allosteric modulation of complement C5 by knob domain peptides JO: Elife http://www.kidney.de/pget.php?&tw=1&pmid=33570492 #FOAvip Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains. To produce high-affinity peptides, we previously isolated autonomous 3-6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug target complement C5. Allosteric mechanisms predominated, with one peptide selectively inhibiting C5 cleavage by the alternative pathway C5 convertase, revealing a targetable mechanistic difference between the classical and alternative pathway C5 convertases. Taking a hybrid biophysical approach, we present C5-knob domain co-crystal structures and, by solution methods, observed allosteric effects propagating >50 A from the binding sites. This study expands the therapeutic scope of C5, presents new inhibitors, and introduces knob domains as new, low molecular weight antibody fragments, with therapeutic potential. Twit Text FOAVip The allosteric modulation of complement C5 by knob domain peptides ????Elife http://www.kidney.de/pget.php?&tw=1&pmid=33570492 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33570492 #FOAvip English Wikipedia <ref>{{Cite pmid|33570492}}</ref> The allosteric modulation of complement C5 by knob domain peptides #MMPMID33570492 Macpherson A; Laabei M; Ahdash Z; Graewert MA; Birtley JR; Schulze ME; Crennell S; Robinson SA; Holmes B; Oleinikovas V; Nilsson PH; Snowden J; Ellis V; Mollnes TE; Deane CM; Svergun D; Lawson AD; van den Elsen JM Elife 2021[Feb]; 10 (ä): ä PMID33570492show ga Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains. To produce high-affinity peptides, we previously isolated autonomous 3-6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug target complement C5. Allosteric mechanisms predominated, with one peptide selectively inhibiting C5 cleavage by the alternative pathway C5 convertase, revealing a targetable mechanistic difference between the classical and alternative pathway C5 convertases. Taking a hybrid biophysical approach, we present C5-knob domain co-crystal structures and, by solution methods, observed allosteric effects propagating >50 A from the binding sites. This study expands the therapeutic scope of C5, presents new inhibitors, and introduces knob domains as new, low molecular weight antibody fragments, with therapeutic potential. |*Drug Discovery[MESH] |Allosteric Regulation/*drug effects[MESH] |Animals[MESH] |Cattle[MESH] |Complement C5/*antagonists & inhibitors/chemistry/metabolism[MESH] |Molecular Docking Simulation[MESH] |Peptides/*chemistry/*pharmacology[MESH]The allosteric modulation of complement C5 by knob domain peptides (epmc).pdf DeepDyve Pubget Overpricing