Structural functionality, catalytic mechanism modeling and molecular allergenicity of phenylcoumaran benzylic ether reductase, an olive pollen (Ole e 12) allergen

J Comput Aided Mol Des. 2013 Oct;27(10):873-95. doi: 10.1007/s10822-013-9686-y. Epub 2013 Oct 24.


Isoflavone reductase-like proteins (IRLs) are enzymes with key roles in the metabolism of diverse flavonoids. Last identified olive pollen allergen (Ole e 12) is an IRL relevant for allergy amelioration, since it exhibits high prevalence among atopic patients. The goals of this study are the characterization of (A) the structural-functionality of Ole e 12 with a focus in its catalytic mechanism, and (B) its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering (1) physicochemical properties and functional-regulatory motifs, (2) sequence analysis, 2-D and 3D structural homology modeling comparative study and molecular docking, (3) conservational and evolutionary analysis, (4) catalytic mechanism modeling, and (5) sequence, structure-docking based B-cell epitopes prediction, while T-cell epitopes were predicted by inhibitory concentration and binding score methods. Structural-based detailed features, phylogenetic and sequences analysis have identified Ole e 12 as phenylcoumaran benzylic ether reductase. A catalytic mechanism has been proposed for Ole e 12 which display Lys133 as one of the conserved residues of the IRLs catalytic tetrad (Asn-Ser-Tyr-Lys). Structure characterization revealed a conserved protein folding among plants IRLs. However, sequence polymorphism significantly affected residues involved in the catalytic pocket structure and environment (cofactor and substrate interaction-recognition). It might also be responsible for IRLs isoforms functionality and regulation, since micro-heterogeneities affected physicochemical and posttranslational motifs. This polymorphism might have large implications for molecular differences in B- and T-cells epitopes of Ole e 12, and its identification may help designing strategies to improve the component-resolving diagnosis and immunotherapy of pollen and food allergy through development of molecular tools.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / chemistry
  • Allergens / immunology*
  • Amino Acid Sequence
  • Catalysis
  • Catalytic Domain
  • Cloning, Molecular
  • Epitopes / chemistry
  • Epitopes / genetics*
  • Epitopes / immunology
  • Humans
  • Models, Molecular
  • Olea / enzymology
  • Olea / immunology
  • Oxidoreductases / chemistry*
  • Oxidoreductases / immunology*
  • Oxidoreductases / metabolism
  • Phylogeny
  • Pollen / enzymology
  • Pollen / immunology
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship


  • Allergens
  • Epitopes
  • Oxidoreductases
  • phenylcoumaran benzylic ether reductase