Indole prenyltransferases comprise a family of enzymes that catalyze the prenylation of l-tryptophan (l-Trp) and other indoles to produce a diverse set of natural products with useful cytotoxic, antimicrobial, and antioxidant properties. CymD from the bacteria <i>Salinispora arenicola</i> catalyzes the reverse N1 prenylation of l-Trp, an unusual reaction given the poor nucleophilicity of the indole nitrogen. CymD utilizes dimethylallyl diphosphate (DMAPP) as the prenyl donor, catalyzing the dissociation of the diphosphate leaving group followed by the nucleophilic attack of the indole nitrogen at the tertiary carbon of the dimethylallyl cation. To elucidate the structural basis of selective indole N-alkylation, the X-ray crystal structures of unliganded CymD, the CymD-l-Trp complex, and the CymD-l-Trp-DMSPP complex (DMSPP is an unreactive analog of DMAPP) were determined. The orientation of l-Trp with respect to DMSPP reveals how the active site contour of CymD serves as a template to direct the reverse prenylation of the indole nitrogen. Activity assays demonstrate the selectivity of CymD for l-Trp and indole as prenyl acceptors, and isothermal titration calorimetry measurements suggest a synergistic relationship between l-Trp and DMSPP binding. Structural studies of other novel indole prenyltransferases are underway to better understand the relationship between primary structure, active site architecture, prenylation regioselectivity, and substrate specificity.

Structural basis of tryptophan reverse N-prenylation catalyzed by CymD

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.