The SEP domain of p47 acts as a reversible competitive inhibitor of cathepsin L

FEBS Lett. 2004 Oct 22;576(3):358-62. doi: 10.1016/j.febslet.2004.09.037.

Abstract

The solution structure of the human p47 SEP domain in a construct comprising residues G1-S2-p47(171-270) was determined by NMR spectroscopy. A structure-derived hypothesis about the domains' function was formulated and pursued in binding experiments with cysteine proteases. The SEP domain was found to be a reversible competitive inhibitor of cathepsin L with a Ki of 1.5 microM. The binding of G1-S2-p47(171-270) to cathepsin L was mapped by biochemical assays and the binding interface was investigated by NMR chemical shift perturbation experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Cathepsin B / chemistry
  • Cathepsin B / metabolism
  • Cathepsin K
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / chemistry
  • Cathepsins / metabolism
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / pharmacology*
  • DNA Primers
  • Humans
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / pharmacology*
  • Protein Structure, Secondary
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Cysteine Proteinase Inhibitors
  • DNA Primers
  • Peptide Fragments
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L
  • CTSK protein, human
  • Cathepsin K