2NW6

Burkholderia cepacia lipase complexed with S-inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.185 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Combined X-ray diffraction and QM/MM study of the Burkholderia cepacia lipase-catalyzed secondary alcohol esterification

Luic, M.Stefanic, Z.Ceilinger, I.Hodoscek, M.Janezic, D.Lenac, T.Asler, I.L.Sepac, D.Tomic, S.

(2008) J Phys Chem B 112: 4876-4883

  • DOI: https://doi.org/10.1021/jp077717u
  • Primary Citation of Related Structures:  
    2NW6

  • PubMed Abstract: 

    To understand the origin of high enantioselectivity of Burkholderia cepacia lipase (BCL) toward secondary alcohol, (R,S)-1-phenoxy-2-hydroxybutane (1), and its ester (E1), we determined the crystal structure of BCL complexed with phosphonate analogue of S-E1 and accomplished a series of MM, MC, and QM/MM studies. We have found that the inhibitor in the S configuration binds into the BCL active site in the same manner as the R isomer, with an important difference: while in case of the R-inhibitor the H-bond between its alcohol oxygen and catalytic His286 can be formed, in the case of the S-inhibitor this is not possible. Molecular modeling for both E1 enantiomers revealed orientations in which all hydrogen bonds characteristic of productive binding are formed. To check the possibility of chemical transformation, four different orientations of the substrate (two for each enantiomer) were chosen, and a series of ab initio QM/MM calculations were accomplished. Starting from the covalent complex, we modeled the ester (E1) hydrolysis and the alcohol (1) esterification. The calculations revealed that ester release is possible starting with all four covalent complexes. Alcohol release from the BCL-E1 complex in which the S-substrate is bound in the same manner as the S-inhibitor in the crystal structure however is not possible. These results show that the crystallographically determined binding modes should be taken with caution when modeling chemical reactions.


  • Organizational Affiliation

    Rudjer Bosković Institute, Bijenicka 54, HR-10000 Zagreb, Croatia, Belupo dd, Danica 5, HR-48000 Koprivnica, Croatia. marija.luic@irb.hr


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lipase320Burkholderia cepaciaMutation(s): 0 
EC: 3.1.1.3
UniProt
Find proteins for P22088 (Burkholderia cepacia)
Explore P22088 
Go to UniProtKB:  P22088
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22088
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.185 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.015α = 90
b = 46.584β = 121.05
c = 84.244γ = 90
Software Package:
Software NamePurpose
CNSrefinement
MAR345dtbdata collection
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-04
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description