2XQ0

Structure of yeast LTA4 hydrolase in complex with Bestatin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

A Leukotriene A(4) Hydrolase-Related Aminopeptidase from Yeast Undergoes Induced Fit Upon Inhibitor Binding.

Helgstrand, C.Hasan, M.Usyal, H.Haeggstrom, J.Z.Thunnissen, M.M.G.M.

(2011) J Mol Biol 406: 120

  • DOI: https://doi.org/10.1016/j.jmb.2010.11.059
  • Primary Citation of Related Structures:  
    2XPY, 2XPZ, 2XQ0

  • PubMed Abstract: 

    Vertebrate leukotriene A(4) hydrolases are bifunctional zinc metalloenzymes with an epoxide hydrolase and an aminopeptidase activity. In contrast, highly homologous enzymes from lower organisms only have the aminopeptidase activity. From sequence comparisons, it is not clear why this difference occurs. In order to obtain more information on the evolutionary relationship between these enzymes and their activities, the structure of a closely related leucine aminopeptidase from Saccharomyces cerevisiae that only shows a very low epoxide hydrolase activity was determined. To investigate the molecular architecture of the active site, the structures of both the native protein and the protein in complex with the aminopeptidase inhibitor bestatin were solved. These structures show a more spacious active site, and the protected cavity in which the labile substrate leukotriene A(4) is bound in the human enzyme is partially obstructed and in other parts is more solvent accessible. Furthermore, the enzyme undergoes induced fit upon binding of the inhibitor bestatin, leading to a movement of the C-terminal domain. The main triggers for the domain movement are a conformational change of Tyr312 and a subtle change in backbone conformation of the PYGAMEN fingerprint region for peptide substrate recognition. This leads to a change in the hydrogen-bonding network pulling the C-terminal domain into a different position. Inasmuch as bestatin is a structural analogue of a leucyl dipeptide and may be regarded as a transition state mimic, our results imply that the enzyme undergoes induced fit during substrate binding and turnover.


  • Organizational Affiliation

    Centre of Molecular Protein Science, Lund University, Getingevägen 60, SE 22100 Lund, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
LEUKOTRIENE A-4 HYDROLASE632Saccharomyces cerevisiaeMutation(s): 0 
EC: 3.3.2.6
UniProt
Find proteins for Q10740 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore Q10740 
Go to UniProtKB:  Q10740
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ10740
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.641α = 90
b = 99.874β = 90
c = 112.651γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-29
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-01-17
    Changes: Data collection
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description