Kelch-like protein

Function Kelch-like proteins (KLHL) contain multiple Kelch motifs. This motif is about 50 residues long and forms a four-stranded β-sheet blade. Six to eight such blades form a circular β-propeller domain. β-propellers are involved in protein-protein interactions. The N-terminal of KLHL contains other protein domains like BTB (Broad-Tramtrack-Bric-a-brac) which is also involved in protein-protein interactions. Disease Somatic mutations in Keap1 were found in lung cancer patients. Relevance KLHL19 (Keap1) interacts with the Neh2 peptide of NRF2. NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target. Structural highlights The interaction of Keap1 with Neh2 is through the first Glu in the latter's ETGE motif.

spinqualitylabelsall models Human Kelch-like protein 1 (Keap1) Kelch domain (grey) complex with NRF2 Neh2 peptide (light green) and sulfate (PDB code 1x2r) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of Kelch-like protein3D Structures of Kelch-like protein

Updated on 05-April-2016

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• Kelch-like protein 2
  • 2xn4 – hKLHL2 Kelch domain – human
    
• Kelch-like protein 3
  • 4chb, 4ch9 – hKLHL3 Kelch domain + serine/threonine protein kinas WNK4 peptide
    
  • 4hxi – hKLHL3 BTB-BACK domain (mutant) + cullin-3 N terminal
    
• Kelch-like protein 7
  • 3ii7 – hKLHL7 Kelch domain
    
• Kelch-like protein 11
  • 3i3n – hKLHL11 BTB-BACK domain
    
  • 4ap2, 4apf – hKLHL11 BTB-BACK domain + cullin-3 N terminal
    
• Kelch-like protein 12
  • 2vpj – hKLHL12 Kelch domain
    
• Kelch-like protein 16 (gigaxonin)
  • 3hve – hKLHL16
    
  • 2ppi – hKLHL16 BTB domain
    
• Kelch-like protein 19 (kelch-like ECH-associated protein 1; Keap1)
  • 1u6d, 1zgk, 4ifj – hKeap1 Kelch domain
    
  • 3zgd – hKeap1 Kelch domain (mutant)
    
  • 4cxi, 4cxj – hKeap1 BTB domain (mutant)
    
  • 1x2j – mKeap1 Kelch domain - mouse
    
• Keap1 complex with peptide
  • 1x2r – mKeap1 Kelch domain + NRF2 Neh2 peptide
    
  • 2z32 – mKeap1 Kelch domain + prothymosin a peptide
    
  • 3ade, 3wdz – mKeap1 Kelch domain + sequestosome-1 peptide
    
  • 2dyh – mKeap1 Kelch domain + NRF2 residues 22-36
    
  • 3wn7 – mKeap1 Kelch domain + NRF2 residues 17-51
    
  • 4ifl, 2flu, 3zgc – hKeap1 Kelch domain + NRF2 Neh2 peptide
    
• Keap1 complex with small molecule
  • 3vng, 3vnh – hKeap1 Kelch domain + oxadiazole derivative
    
  • 4ifn – hKeap1 Kelch domain + quinoline derivative
    
  • 4l7b, 4l7c, 4l7d 4n1b – hKeap1 Kelch domain (mutant) + quinoline derivative
    
  • 4in4 – hKeap1 Kelch domain + inhibitor
    
  • 4iqk – hKeap1 Kelch domain (mutant) + inhibitor
    
  • 4cxt – hKeap1 BTB domain (mutant) + antagonist