1HUC

THE REFINED 2.15 ANGSTROMS X-RAY CRYSTAL STRUCTURE OF HUMAN LIVER CATHEPSIN B: THE STRUCTURAL BASIS FOR ITS SPECIFICITY


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Observed: 0.164 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity.

Musil, D.Zucic, D.Turk, D.Engh, R.A.Mayr, I.Huber, R.Popovic, T.Turk, V.Towatari, T.Katunuma, N.Bode, W.

(1991) EMBO J 10: 2321-2330

  • DOI: https://doi.org/10.1002/j.1460-2075.1991.tb07771.x
  • Primary Citation of Related Structures:  
    1HUC

  • PubMed Abstract: 

    From the lysosomal cysteine proteinase cathepsin B, isolated from human liver in its two-chain form, monoclinic crystals were obtained which contain two molecules per asymmetric unit. The molecular structure was solved by a combination of Patterson search and heavy atom replacement methods (simultaneously with rat cathepsin B) and refined to a crystallographic R value of 0.164 using X-ray data to 2.15 A resolution. The overall folding pattern of cathepsin B and the arrangement of the active site residues are similar to the related cysteine proteinases papain, actinidin and calotropin DI. 166 alpha-carbon atoms out of 248 defined cathepsin B residues are topologically equivalent (with an r.m.s. deviation of 1.04 A) with alpha-carbon atoms of papain. However, several large insertion loops are accommodated on the molecular surface and modify its properties. The disulphide connectivities recently determined for bovine cathepsin B by chemical means were shown to be correct. Some of the primed subsites are occluded by a novel insertion loop, which seems to favour binding of peptide substrates with two residues carboxy-terminal to the scissile peptide bond; two histidine residues (His110 and His111) in this "occluding loop' provide positively charged anchors for the C-terminal carboxylate group of such polypeptide substrates. These structural features explain the well-known dipeptidyl carboxypeptidase activity of cathepsin B. The other subsites adjacent to the reactive site Cys29 are relatively similar to papain; Glu245 in the S2 subsite favours basic P2-side chains. The above mentioned histidine residues, but also the buried Glu171 might represent the group with a pKa of approximately 5.5 near the active site, which governs endo- and exopeptidase activity. The "occluding loop' does not allow cystatin-like protein inhibitors to bind to cathepsin B as they do to papain, consistent with the reduced affinity of these protein inhibitors for cathepsin B compared with the related plant enzymes.


  • Organizational Affiliation

    Max-Planck-Institut für Biochemie, Martinsried, FRG.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CATHEPSIN B
A, C
47Homo sapiensMutation(s): 0 
EC: 3.4.22.1
UniProt & NIH Common Fund Data Resources
Find proteins for P07858 (Homo sapiens)
Explore P07858 
Go to UniProtKB:  P07858
PHAROS:  P07858
GTEx:  ENSG00000164733 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07858
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CATHEPSIN B
B, D
205Homo sapiensMutation(s): 0 
EC: 3.4.22.1
UniProt & NIH Common Fund Data Resources
Find proteins for P07858 (Homo sapiens)
Explore P07858 
Go to UniProtKB:  P07858
PHAROS:  P07858
GTEx:  ENSG00000164733 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07858
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Observed: 0.164 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.23α = 90
b = 34.16β = 102.9
c = 85.56γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
EREFrefinement
X-PLORrefinement
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1995-01-26
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance