Crystal structure of human cathepsin V

Biochemistry. 2000 Oct 17;39(41):12543-51. doi: 10.1021/bi000951p.


Cathepsin V is a lysosomal cysteine protease that is expressed in the thymus, testis and corneal epithelium. We have determined the 1.6 A resolution crystal structure of human cathepsin V associated with an irreversible vinyl sulfone inhibitor. The fold of this enzyme is similar to the fold adopted by other members of the papain superfamily of cysteine proteases. This study provides a framework for understanding the structural basis for cathepsin V's activity and will aid in the design of inhibitors of this enzyme. A comparison of cathepsin V's active site with the active sites of related proteases revealed a number of differences, especially in the S2 and S3 subsites, that could be exploited in identifying specific cathepsin V inhibitors or in identifying inhibitors of other cysteine proteases that would be selective against cathepsin V.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / chemistry*
  • Cathepsins / genetics
  • Cathepsins / isolation & purification
  • Computer Simulation
  • Crystallography, X-Ray
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / isolation & purification
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry
  • Humans
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Substrate Specificity
  • Sulfones / chemical synthesis
  • Sulfones / chemistry


  • Cysteine Proteinase Inhibitors
  • Piperazines
  • Sulfones
  • APC 3316
  • Cathepsins
  • Cysteine Endopeptidases
  • CTSV protein, human

Associated data

  • PDB/1FH0