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Structure‐Guided Mutagenesis Reveals the Catalytic Residue that Controls the Regiospecificity of C6‐Indole Prenyltransferases
- Source :
- ChemCatChem
- Publication Year :
- 2023
- Publisher :
- Wiley, 2023.
-
Abstract
- Indole is a significant structural moiety and functionalization of the C–H bond in indole-containing molecules expands their chemical space, and modifies their properties and/or activities. Indole prenyltransferases (IPTs) catalyze the direct regiospecific installation of prenyl, C5 carbon units, on indole-derived compounds. IPTs have shown relaxed substrate flexibility enabling them to be used as tools for indole functionalization. However, the mechanism by which certain IPTs target a specific carbon position is not fully understood. Herein, we use structure-guided site-directed mutagenesis, in vitro enzymatic reactions, kinetics and structural-elucidation of analogs to verify the key catalytic residues that control the regiospecificity of all characterized regiospecific C6 IPTs. Our results also demonstrate that substitution of PriB_His312 to Tyr leads to the synthesis of analogs prenylated at different positions than C6. This work contributes to understanding of how certain IPTs can access a challenging position in indole-derived compounds.
Details
- ISSN :
- 18673899 and 18673880
- Database :
- OpenAIRE
- Journal :
- ChemCatChem
- Accession number :
- edsair.doi.dedup.....96c045822fd12eab4f0a01389f55c3b1