High-Resolution Snapshots of Proteasome Inhibitors in Action Revise Inhibition Paradigms and Inspire Next-Generation Inhibitor Design.
New high-resolution crystal structures reported by Schrader and colleagues refine our understanding of how peptide epoxyketone anticancer drugs inactivate their target: the human proteasome. These findings provide important clues for the design of next-generation proteasome inhibitor drugs.
Department of Pharmaceutical Sciences, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536-0596, USA.
Kimberly
K
Carmony
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
Wooin
W
Lee
Department of Pharmaceutical Sciences, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536-0596, USA.
Kyung Bo
KB
Kim
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000378:metabolism*
D000970:Antineoplastic Agents; C554738:ONX 0912; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex
drug design; epoxyketone; oprozomib; proteasome inhibitors; proteasome structures