Structure of cruzipain/cruzain inhibitors isolated from Bauhinia bauhinioides seeds

Biol Chem. 2001 May;382(5):847-52. doi: 10.1515/BC.2001.103.

Abstract

The saline extract of Bauhinia bauhinioides dry seeds was shown to inhibit cruzipain, a cysteine proteinase from Trypanosoma cruzi. The inhibitory activity was assigned to a protein with 164 amino acid residues and molecular mass of 18 034 Da that was purified by chromatography on DEAE-Sephadex, trypsin-Sepharose (removal of trypsin inhibitors), Mono Q and a reversed-phase C4 column. The primary structure is homologous to other plant Kunitz-type inhibitors, but it lacks cysteine residues and therefore the disulfide bridges. No methionine residue was identified by amino acid sequencing. The inhibition of cruzipain fits into a slow-tight binding mechanism with a low dissociation constant (Ki 1.2 nM). The studied Bauhinia protein also inhibits cruzain (Ki 0.3 nM), a C-terminally truncated recombinant species of cruzipain. Cathepsin L, a cysteine proteinase with high homology to cruzipain, is also inhibited (Ki 0.22 nM), but not cathepsin B, papain, bromelain or ficin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cysteine Endopeptidases / drug effects
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / isolation & purification
  • Kinetics
  • Molecular Sequence Data
  • Molecular Structure
  • Plant Proteins / chemistry*
  • Plant Proteins / isolation & purification
  • Protozoan Proteins / antagonists & inhibitors*
  • Seeds / chemistry
  • Sequence Alignment

Substances

  • Cysteine Proteinase Inhibitors
  • Plant Proteins
  • Protozoan Proteins
  • Cysteine Endopeptidases
  • cruzain, Trypanosoma cruzi
  • cruzipain