Active center differences between cathepsins L and B: the S1 binding region

FEBS Lett. 1988 Feb 8;228(1):128-30. doi: 10.1016/0014-5793(88)80600-8.

Abstract

The substrate peptide bond cleaved by cathepsins B and L is determined not by the amino acid contributing the carboxyl group to this bond as in the case of serine proteases but rather by the presence of a neighboring amino acid with a large hydrophobic side chain. From a study of the inhibitory potency in a series, Cbz-Phe-X-CHN2, in which Phe promotes binding at S2 (terminology of [(1968) Biochem. Biophys. Res. Commun. 32, 898-902]) while the amino acid X probes S1, it is shown that this region of cathepsin L also has the ability to accommodate large hydrophobic side chains. In this respect cathepsin L differs from cathepsin B. Thus Cbz-Phe-Tyr(O-t-Bu)CHN2 inactivates cathepsin L with a rate 2.5 x 10(4) greater than that for cathepsin B.

MeSH terms

  • Amino Acids / physiology
  • Animals
  • Binding Sites
  • Cathepsin B* / antagonists & inhibitors
  • Cathepsin L
  • Cathepsins* / antagonists & inhibitors
  • Cysteine Endopeptidases
  • Endopeptidases*
  • Indicators and Reagents
  • Liver / enzymology
  • Rats

Substances

  • Amino Acids
  • Indicators and Reagents
  • Cathepsins
  • Endopeptidases
  • Cysteine Endopeptidases
  • Cathepsin B
  • Cathepsin L
  • Ctsl protein, rat