Effects of α-kainic acid, domoic acid and their derivatives on a molluscan giant neuron sensitive to β-hydroxy-l-glutamic acid

1984 ◽  
Vol 102 (2) ◽  
pp. 325-332 ◽  
Author(s):  
Hiroshi Takeuchi ◽  
Kazuko Watanabe ◽  
Kyosuke Nomoto ◽  
Yasufumi Ohfune ◽  
Tsunematsu Takemoto
Keyword(s):  
Glutamic Acid ◽  
Kainic Acid ◽  
Domoic Acid ◽  
Giant Neuron

scholarly journals Algal Neurotoxin Biosynthesis Repurposes the Terpene Cyclase Structural Fold Into an N-prenyltransferase

2020 ◽  
Author(s):  
Jonathan R. Chekan ◽  
Shaun M. K. McKinnie ◽  
Joseph P. Noel ◽  
Bradley S. Moore
Keyword(s):  
Crystal Structure ◽  
Glutamic Acid ◽  
Kainic Acid ◽  
Domoic Acid ◽  
Marine Algae ◽  
Single Amino Acid ◽  
Binding Motif ◽  
Rational Engineering ◽  
New Family ◽  
Terpene Cyclase

AbstractPrenylation is a common biological reaction in all domains of life whereupon prenyl diphosphate donors transfer prenyl groups onto small molecules as well as large proteins. The enzymes that catalyze these biotransformations are structurally distinct from ubiquitous terpene cyclases that instead assemble terpene molecules via intramolecular rearrangements. Herein we report the structure and molecular details of a new family of prenyltransferases from marine algae that repurposes the terpene cyclase structural fold for the N-prenylation of glutamic acid during the biosynthesis of the potent neurochemicals domoic acid and kainic acid. We solved the X-ray crystal structure of the prenyltransferase found in domoic acid biosynthesis, DabA, and show distinct active site binding modifications that remodel the canonical Mg2+-binding motif. We then applied our structural knowledge of DabA and a homologous enzyme from the kainic acid biosynthetic pathway, KabA, to alter their isoprene donor specificities (geranyl versus dimethylallyl diphosphate) by a single amino acid switch. While the diatom DabA and seaweed KabA enzymes share a common evolutionary lineage, they are distinct from all other terpene cyclases, suggesting a very distant ancestor.SignificanceDomoic acid is a neurotoxin produced by marine algae that readily bioaccumulates in shellfish and significantly impacts both human and animal life. The first committed step of the biosynthesis of domoic acid is the N-prenylation of L-glutamic acid by the enzyme DabA. By solving the crystal structure of DabA, we demonstrate that this enzyme has repurposed the common terpene cyclase fold to catalyze an extremely unusual reaction, N-prenylation of an unactivated primary amine. Application of these structural insights enabled rational engineering of two N-prenyltransferase enzymes to accept alternative prenyl donors. Ultimately, these results not only expand the scope of reactions catalyzed by a terpene cyclase family member, but will help inform future domoic acid environmental monitoring efforts.

Effects of L-glutamic acid and kainic acid on central cardiovascular control

1979 ◽  
Vol 60 (1) ◽  
pp. 91-94 ◽  
Author(s):  
Jacques Chelly ◽  
Jean C. Kouyoumdjian ◽  
Paule Mouillé ◽  
Anne-Marie Huchet ◽  
Henri Schmitt
Keyword(s):  
Glutamic Acid ◽  
Kainic Acid ◽  
Cardiovascular Control

Reduced neuroexcitatory effect of domoic acid following mossy fiber denervation of the rat dorsal hippocampus: further evidence that toxicity of domoic acid involves kainate receptor activation

1989 ◽  
Vol 67 (8) ◽  
pp. 904-908 ◽  
Author(s):  
Guy Debonnel ◽  
Michel Weiss ◽  
Claude de Montigny
Keyword(s):  
Kainic Acid ◽  
Prince Edward Island ◽  
Domoic Acid ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Excitatory Amino Acid ◽  
Dorsal Hippocampus ◽  
Receptor Activation ◽  
Kainate Receptors ◽  
Quisqualic Acid

Domoic acid, an excitatory amino acid structurally related to kainic acid, has been shown to be responsible for the severe intoxication presented, in 1987, by more than one hundred and fifty people having eaten mussels grown in Prince Edward Island (Canada). Unitary extracellular recordings were obtained from pyramidal neurons of the CA3 region of the rat dorsal hippocampus. The excitatory effects of microiontophoretic applications of domoic acid and of the agonists of the two other subtypes of glutamatergic receptors, quisqualate and N-methyl-D-aspartate, were compared on intact and colchicine-lesioned sides. Similar to what has been previously found for kainate, the colchicine lesion of the mossy fiber projections induced a 95% decrease of the neuronal responsiveness to domoic acid, whereas the effect of quisqualate was unchanged and that of N-methyl-D-aspartate was only slightly decreased. These results provide further electrophysiological evidence that domoic acid is a potent agonist of kainate receptors and that it may produce its neuroexcitatory and neurotoxic effects, in the hippocampal CA3 region, through activation of kainate receptors located on the mossy fiber terminals.Key words: domoic acid, kainic acid, glutamic acid, N-methyl-D-aspartic acid, quisqualic acid, dorsal hippocampus, neurotoxins.

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