1THE

CRYSTAL STRUCTURES OF RECOMBINANT RAT CATHEPSIN B AND A CATHEPSIN B-INHIBITOR COMPLEX: IMPLICATIONS FOR STRUCTURE-BASED INHIBITOR DESIGN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Work: 0.170 
  • R-Value Observed: 0.170 

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This is version 1.3 of the entry. See complete history


Literature

Crystal structures of recombinant rat cathepsin B and a cathepsin B-inhibitor complex. Implications for structure-based inhibitor design.

Jia, Z.Hasnain, S.Hirama, T.Lee, X.Mort, J.S.To, R.Huber, C.P.

(1995) J Biol Chem 270: 5527-5533

  • DOI: https://doi.org/10.1074/jbc.270.10.5527
  • Primary Citation of Related Structures:  
    1CPJ, 1CTE, 1THE

  • PubMed Abstract: 

    The lysosomal cysteine proteinase cathepsin B (EC 3.4.22.1) plays an important role in protein catabolism and has also been implicated in various disease states. The crystal structures of two forms of native recombinant rat cathepsin B have been determined. The overall folding of rat cathepsin B was shown to be very similar to that of the human liver enzyme. The structure of the native enzyme containing an underivatized active site cysteine (Cys29) showed the active enzyme conformation to be similar to that determined previously for the oxidized form. In a second structure Cys29 was derivatized with the reversible blocking reagent pyridyl disulfide. In this structure large side chain conformational changes were observed for the two key catalytic residues Cys29 and His199, demonstrating the potential flexibility of these side chains. In addition the structure of the complex between rat cathepsin B and the inhibitor benzyloxycarbonyl-Arg-Ser(O-Bzl) chloromethylketone was determined. The complex structure showed that very little conformational change occurs in the enzyme upon inhibitor binding. It also allowed visualization of the interaction between the enzyme and inhibitor. In particular the interaction between Glu245 and the P2 Arg residue was clearly demonstrated, and it was found that the benzyl group of the P1 substrate residue occupies a large hydrophobic pocket thought to represent the S'1 subsite. This may have important implications for structure-based design of cathepsin B inhibitors.


  • Organizational Affiliation

    Institute for Biological Sciences, National Research Council of Canada, Ottawa.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cathepsin B
A, B
260Rattus norvegicusMutation(s): 0 
Gene Names: CDNACtsb
EC: 3.4.22.1
UniProt
Find proteins for P00787 (Rattus norvegicus)
Explore P00787 
Go to UniProtKB:  P00787
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00787
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0E6
Query on 0E6

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
amino{[(4S)-4-{[(benzyloxy)carbonyl]amino}-5-{[(2S)-1-(benzyloxy)-4-chloro-3-oxobutan-2-yl]amino}-5-oxopentyl]amino}met haniminium
C25 H33 Cl N5 O5
ZCPUCLRLZWEDRC-SFTDATJTSA-O
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Work: 0.170 
  • R-Value Observed: 0.170 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.11α = 90
b = 90.15β = 97.24
c = 62.31γ = 90
Software Package:
Software NamePurpose
SDMSdata collection
X-PLORmodel building
X-PLORrefinement
SDMSdata reduction
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1996-03-10
    Type: Initial release
  • Version 1.1: 2008-03-24
    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: 2012-12-12
    Changes: Other