Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes.
Journal, issue, pages	Nat Commun, Vol. 8, Issue 1, Page 1692, Year 2017
Publish date	Nov 22, 2017
Authors	Ruda de Luna Almeida Santos / Lin Bai / Pradeep K Singh / Naoka Murakami / Hao Fan / Wenhu Zhan / Yingrong Zhu / Xiuju Jiang / Kaiming Zhang / Jean Pierre Assker / Carl F Nathan / Huilin Li / Jamil Azzi / Gang Lin /
PubMed Abstract	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 ...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 β5i subunit while sparing the constitutive β5c subunit. Here we report β5i-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 β5i and β6 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, β5i-selective inhibitors may be useful for treatment of diseases involving activated or neoplastic B cells or activated T cells.
External links	Nat Commun / PubMed:29167449 / PubMed Central
Methods	EM (single particle)
Resolution	3.8 Å
Structure data	7010 6avo EMDB-7010, PDB-6avo: Cryo-EM structure of human immunoproteasome with a novel noncompetitive inhibitor that selectively inhibits activated lymphocytes Method: EM (single particle) / Resolution: 3.8 Å
Chemicals	ChemComp-BZ7: N~1~-{2-[([1,1'-biphenyl]-3-carbonyl)amino]ethyl}-N~4~-tert-butyl-N~2~-(3-phenylpropanoyl)-L-aspartamide
Source	homo sapiens (human)
Keywords	HYDROLASE/HYDROLASE INHIBITOR / inhibitor / complex / immunoproteasome / HYDROLASE-HYDROLASE INHIBITOR complex