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

• Published in: Journal of computer-aided molecular design Vol. 27; no. 10; pp. 873 - 895
• Main Authors: Jimenez-Lopez, Jose C., Kotchoni, Simeon O., Hernandez-Soriano, Maria C., Gachomo, Emma W., Alché, Juan D.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2013; Springer Nature B.V
• Subjects: Allergens; Allergens - chemistry; Allergens - immunology; Allergies; Amino Acid Sequence; Animal Anatomy; Catalysis; Catalytic Domain; Chemistry; Chemistry and Materials Science; Cloning, Molecular; Comparative studies; Computer Applications in Chemistry; Enzymes; Epitopes - chemistry; Epitopes - genetics; Epitopes - immunology; Flavonoids; Food allergies; Histology; Humans; Immunotherapy; Metabolites; Models, Molecular; Molecular biology; Morphology; Olea - enzymology; Olea - immunology; Oxidoreductases - chemistry; Oxidoreductases - immunology; Oxidoreductases - metabolism; Phylogeny; Physical Chemistry; Physicochemical properties; Pollen; Pollen - enzymology; Pollen - immunology; Proteins; Sequence Homology, Amino Acid; Structure-Activity Relationship; Isoflavone reductase; Olive; Flavonoids; Homology modeling; Polyphenols; NAD(P)H; Pollen; Sequence polymorphism; Electrostatic potential; Molecular docking; Allergen; B- and T-cell epitopes
• ISSN: 0920-654X; 1573-4951
• DOI: 10.1007/s10822-013-9686-y

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.