2flu
From Proteopedia
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Crystal Structure of the Kelch-Neh2 Complex
Overview
Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state, levels of Nrf2, a bZIP transcription factor, in response to oxidative, stress. We have determined the structure of the Kelch domain of Keap1, bound to a 16-mer peptide from Nrf2 containing a highly conserved DxETGE, motif. The Nrf2 peptide contains two short antiparallel beta-strands, connected by two overlapping type I beta-turns stabilized by the aspartate, and threonine residues. The beta-turn region fits into a binding pocket on, the top face of the Kelch domain and the glutamate residues form multiple, hydrogen bonds with highly conserved residues in Keap1. Mutagenesis, experiments confirmed the role of individual amino acids for binding of, Nrf2 to Keap1 and for Keap1-mediated repression of Nrf2-dependent gene, expression. Our results provide a detailed picture of how a BTB-Kelch, substrate adaptor protein binds to its cognate substrate and will enable, the rational design of novel chemopreventive agents.
About this Structure
2FLU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling., Lo SC, Li X, Henzl MT, Beamer LJ, Hannink M, EMBO J. 2006 Aug 9;25(15):3605-17. Epub 2006 Aug 3. PMID:16888629
Page seeded by OCA on Mon Nov 12 22:07:19 2007
