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

Jimenez-Lopez, Jose C., Kotchoni, Simeon O., Hernandez-Soriano, Maria C., Gachomo, Emma W. and Alche, Juan D. (2013) Structural functionality, catalytic mechanism modeling and molecular allergenicity of phenylcoumaran benzylic ether reductase, an olive pollen (Ole e 12) allergen. Journal of Computer-Aided Molecular Design, 27 10: 873-895. doi:10.1007/s10822-013-9686-y


Author Jimenez-Lopez, Jose C.
Kotchoni, Simeon O.
Hernandez-Soriano, Maria C.
Gachomo, Emma W.
Alche, Juan D.
Title Structural functionality, catalytic mechanism modeling and molecular allergenicity of phenylcoumaran benzylic ether reductase, an olive pollen (Ole e 12) allergen
Journal name Journal of Computer-Aided Molecular Design   Check publisher's open access policy
ISSN 0920-654X
1573-4951
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1007/s10822-013-9686-y
Open Access Status Not Open Access
Volume 27
Issue 10
Start page 873
End page 895
Total pages 23
Place of publication Dordrecht, Netherlands
Publisher Springer
Abstract 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.
Keyword Allergen
B- and T-cell epitopes
Electrostatic potential
Flavonoids
Homology modeling
Isoflavone reductase
Molecular docking
NAD(P)H
Olive
Pollen
Polyphenols
Sequence polymorphism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Agriculture and Food Sciences
Official 2014 Collection
 
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