Many polyphenolic natural products from plants and fungi have properties beneficial to human health (e.g., antimicrobial, antitumor, and anti-inflammatory properties) but are rhamnosylated, which severely limits their bioavailability because they cannot be digested by enzymes endogenous to humans. RHA-P is a catalytically efficient α-L-rhamnosidase that selectively cleaves a terminal rhamnose from a polyphenolic moiety, thereby increasing its bioavailability. This work reports the 2.2 Å resolution crystal structure of RHA-P. The final model shows highly conserved substrate- and calcium-binding residues in the active site in comparison to BT0986, the only crystallized homolog of RHA-P (pdbID: 5MQN). RHA-P has a relatively hydrophobic binding pocket, which corroborates the specificity of RHA-P for glycosylated aryl compounds such as hesperidin, naringin, and rutin. An additional loop inserted into the active site RHA-P also likely influences substrate specificity. Ongoing work aims to explore the structure-function relationship further by determining ligand-bound structures to inform subsequent directed evolution of RHA-P for industrial applications in the production of bioavailable polyphenols.

Improving bioavailability by selective pruning of glycosylated molecules: The crystal structure of a Rrhamnosidase from novosphingobium sp. PP1Y

2019 Spring National Meeting

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