6mg4: Difference between revisions
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==Structure of full-length human lambda-6A light chain JTO== | |||
<StructureSection load='6mg4' size='340' side='right'caption='[[6mg4]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6mg4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MG4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6mg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mg4 OCA], [https://pdbe.org/6mg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mg4 RCSB], [https://www.ebi.ac.uk/pdbsum/6mg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mg4 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In Ig light-chain (LC) amyloidosis (AL), the unique antibody LC protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. As a step toward developing treatments for AL patients with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, we introduce small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which can slow or stop the amyloidogenicity cascade at its origin. A protease-coupled fluorescence polarization-based high-throughput screen was employed to identify small molecules that kinetically stabilize LCs. NMR and X-ray crystallographic data demonstrate that at least one structural family of hits bind at the LC-LC dimerization interface within full-length LCs, utilizing variable-domain residues that are highly conserved in most AL patients. Stopping the amyloidogenesis cascade at the beginning is a proven strategy to ameliorate postmitotic tissue degeneration. | |||
Stabilization of amyloidogenic immunoglobulin light chains by small molecules.,Morgan GJ, Yan NL, Mortenson DE, Rennella E, Blundon JM, Gwin RM, Lin CY, Stanfield RL, Brown SJ, Rosen H, Spicer TP, Fernandez-Vega V, Merlini G, Kay LE, Wilson IA, Kelly JW Proc Natl Acad Sci U S A. 2019 Apr 10. pii: 1817567116. doi:, 10.1073/pnas.1817567116. PMID:30971495<ref>PMID:30971495</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6mg4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Kelly JW]] | |||
[[Category: Morgan GJ]] | |||
[[Category: Mortenson DE]] | |||
[[Category: Stanfield RL]] | |||
[[Category: Wilson IA]] | |||
[[Category: Yan NL]] |