1FH0

CRYSTAL STRUCTURE OF HUMAN CATHEPSIN V COMPLEXED WITH AN IRREVERSIBLE VINYL SULFONE INHIBITOR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


This is version 1.7 of the entry. See complete history


Literature

Crystal structure of human cathepsin V.

Somoza, J.R.Zhan, H.Bowman, K.K.Yu, L.Mortara, K.D.Palmer, J.T.Clark, J.M.McGrath, M.E.

(2000) Biochemistry 39: 12543-12551

  • DOI: https://doi.org/10.1021/bi000951p
  • Primary Citation of Related Structures:  
    1FH0

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Axys Pharmaceuticals, Inc., 385 Oyster Point Boulevard, Suite 1, South San Francisco, California 94080, USA. john_somoza@axyspharm.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CATHEPSIN V
A, B
221Homo sapiensMutation(s): 2 
EC: 3.4.22
UniProt & NIH Common Fund Data Resources
Find proteins for O60911 (Homo sapiens)
Explore O60911 
Go to UniProtKB:  O60911
PHAROS:  O60911
GTEx:  ENSG00000136943 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60911
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0IW
Query on 0IW

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
Nalpha-[(4-methylpiperazin-1-yl)carbonyl]-N-[(3S)-1-phenyl-5-(phenylsulfonyl)pentan-3-yl]-L-phenylalaninamide
C32 H40 N4 O4 S
VZSXPUDQSLKVIR-JDXGNMNLSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Biologically Interesting Molecules (External Reference) 1 Unique
Entity ID: 2
IDChains NameType/Class2D Diagram3D Interactions
PRD_000325 (0IW)
Query on PRD_000325
C [auth A],
E [auth B]
MePip-Phe-HphVSPhPeptide-like / Inhibitor
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.198 
  • Space Group: P 64 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.7α = 90
b = 104.7β = 90
c = 179.2γ = 120
Software Package:
Software NamePurpose
MAR345data collection
DENZOdata reduction
SCALEPACKdata scaling
EPMRphasing
CNXrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2001-07-30 
  • Deposition Author(s): Somoza, J.R.

Revision History  (Full details and data files)

  • Version 1.0: 2001-07-30
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2011-10-12
    Changes: Non-polymer description
  • Version 1.4: 2013-02-27
    Changes: Other
  • Version 1.5: 2017-10-04
    Changes: Refinement description
  • Version 1.6: 2021-11-03
    Changes: Database references, Derived calculations
  • Version 1.7: 2024-03-13
    Changes: Data collection, Source and taxonomy, Structure summary