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Hevein (Hev b 6.02) is a major IgE-binding allergen in natural rubber latex and manufactured products. Both tryptophans (Trp²¹ and Trp²³) of the hevein molecule were chemically modified with BNPS-skatole (2-nitrophenylsulfenyl-3-methyl-3^′-bromoindolenine); derivatized allergen failed to significantly inhibit binding of serum IgE in ELISA assays. Similarly, skin prick tests showed that hevein-positive patients gave no response with the modified allergen. Dot blot experiments carried out with anti-hevein mono- and polyclonal antibodies confirmed the importance of Trp²¹ and Trp²³ for antibody-recognition, and demonstrated the specific cross-reactivity of other molecules containing hevein-like domains. We also report the structure of Hev b 6.02 at an extended resolution (1.5Å) and compare its surface properties around Trp residues with those of similar regions in other allergens. Overall our results indicate that …