Structural and Functional Characterization of the N-Prenyltransferase DsKabA in Algal Neurotoxin Biosynthesis.

Authors

Wei-Jia Huang, Sheng-Chia Chen, I-Weh Chien, Chia-Hsin Lin, Jia-Yi Zhou, Bo-Yan Guo, San-Chi Chang, Sheng-Wei Lin, Chun-Hua Hsu

Published in

Journal of agricultural and food chemistry. Volume 74. Issue 44. Pages 34989-35002. Nov 11, 2026.

Abstract

Kainic acid (KA) is a neuroactive natural product from the red alga Digenea simplex. Its biosynthesis begins with DsKabA, an N-prenyltransferase that converts l-glutamate and dimethylallyl pyrophosphate into prekainic acid, the first committed intermediate. Here, we combined LC-MS activity assays, X-ray crystallography, SAXS, molecular docking, ITC, MD simulations, and mutagenesis to characterize DsKabA. Product analysis confirmed prekainic acid formation, and kinetic measurements yielded apparent Km values of 1.03 ± 0.16 μM for DMAPP and 52.25 ± 1.61 mM for l-Glu. The 2.85 Å apo structure revealed open and closed conformations involving the α7-loop-α8 region near the active site. Docking, ITC, and mutagenesis support Mg2+-dependent donor binding, ordered l-Glu association, and roles for Y403, H406, E407, M114, and M118 in catalysis and prenyl-donor recognition. These findings provide structural and mechanistic insight into the first committed step of KA biosynthesis.

PMID:
43012693
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.

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