Crystal structures of reversible ketone-Based inhibitors of the cysteine protease cruzain

Bioorg Med Chem. 2003 Jan 2;11(1):21-9. doi: 10.1016/s0968-0896(02)00427-3.

Abstract

The crystal structures of two hydroxymethyl ketone inhibitors complexed to the cysteine protease cruzain have been determined at 1.1 and 1.2 A resolution, respectively. These high resolution crystal structures provide the first structures of non-covalent inhibitors bound to cruzain. A series of compounds were prepared and tested based upon the structures providing further insight into the key binding interactions.

MeSH terms

  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Ketones / chemistry*
  • Ketones / metabolism
  • Ketones / pharmacology*
  • Models, Molecular
  • Protein Binding
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / metabolism
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology
  • Trypanosoma cruzi / enzymology

Substances

  • Cysteine Proteinase Inhibitors
  • Ketones
  • Protozoan Proteins
  • Sulfhydryl Compounds
  • Cysteine Endopeptidases
  • cruzain, Trypanosoma cruzi

Associated data

  • PDB/1ME3
  • PDB/1ME4