title: Structural functionality, catalytic mechanism modeling and molecular allergenicity of phenylcoumaran benzylic ether reductase, an olive pollen (Ole e 12) allergen.
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.
authors.affiliation: Department of Biochemistry, Cell and Molecular Biology of Plants, Estación Experimental del Zaidín, Spanish National Research Council (CSIC), Profesor Albareda 1, 18008, Granada, Spain, josecarlos.jimenez@eez.csic.es.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Jimenez-Lopez
authors.forename: Simeon O
authors.initials: SO
authors.lastname: Kotchoni
authors.forename: Maria C
authors.initials: MC
authors.lastname: Hernandez-Soriano
authors.forename: Emma W
authors.initials: EW
authors.lastname: Gachomo
authors.forename: Juan D
authors.initials: JD
authors.lastname: Alché
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D002384:Catalysis; D020134:Catalytic Domain; D003001:Cloning, Molecular; D000939:Epitopes / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D031658:Olea / Q000201:enzymology / Q000276:immunology; D010088:Oxidoreductases / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D010802:Phylogeny; D011058:Pollen / Q000201:enzymology / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D000485:Allergens; D000939:Epitopes; D010088:Oxidoreductases; C118150:phenylcoumaran benzylic ether reductase