4E3T

Round 18 Arylesterase Variant of Phosphotriesterase with Bound Transition State Analog


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.175 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme

Tokuriki, N.Jackson, C.J.Afriat-Jurnou, L.Wyganowski, K.T.Tang, R.Tawfik, D.S.

(2012) Nat Commun 3: 1257-1257

  • DOI: https://doi.org/10.1038/ncomms2246
  • Primary Citation of Related Structures:  
    4E3T, 4GY0, 4GY1

  • PubMed Abstract: 

    Optimization processes, such as evolution, are constrained by diminishing returns-the closer the optimum, the smaller the benefit per mutation, and by tradeoffs-improvement of one property at the cost of others. However, the magnitude and molecular basis of these parameters, and their effect on evolutionary transitions, remain unknown. Here we pursue a complete functional transition of an enzyme with a >10(9)-fold change in the enzyme's selectivity using laboratory evolution. We observed strong diminishing returns, with the initial mutations conferring >25-fold higher improvements than later ones, and asymmetric tradeoffs whereby the gain/loss ratio of the new/old activity decreased 400-fold from the beginning of the trajectory to its end. We describe the molecular basis for these phenomena and suggest they have an important role in shaping natural proteins. These findings also suggest that the catalytic efficiency and specificity of many natural enzymes may be far from their optimum.


  • Organizational Affiliation

    Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4. tokuriki@msl.ubc.ca


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphotriesterase
A, B
333Brevundimonas diminutaMutation(s): 0 
EC: 3.1.8.1
UniProt
Find proteins for P0A434 (Brevundimonas diminuta)
Explore P0A434 
Go to UniProtKB:  P0A434
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0A434
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.771α = 90
b = 85.975β = 90
c = 88.727γ = 90
Software Package:
Software NamePurpose
DNAdata collection
MOLREPphasing
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-01-23
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description