6VKZ

Crystal Structure of the N-prenyltransferase DabA in Complex with GSPP and Mg2+

6VKZ の概要

• エントリーDOI: 10.2210/pdb6vkz/pdb
• 分子名称: DabA, MAGNESIUM ION, GERANYL S-THIOLODIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: prenyltransferase, terpene cyclase, transferase
• 由来する生物種: Pseudo-nitzschia multiseries
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51948.81

構造登録者

Chekan, J.R.,Noel, J.P.,Moore, B.S. (登録日: 2020-01-22, 公開日: 2020-04-08, 最終更新日: 2024-03-06)

主引用文献

Chekan, J.R.,McKinnie, S.M.K.,Noel, J.P.,Moore, B.S.
Algal neurotoxin biosynthesis repurposes the terpene cyclase structural fold into anN-prenyltransferase.
Proc.Natl.Acad.Sci.USA, 117:12799-12805, 2020

PubMed Abstract: Prenylation is a common biological reaction in all domains of life wherein prenyl diphosphate donors transfer prenyl groups onto small molecules as well as large proteins. The enzymes that catalyze these reactions are structurally distinct from ubiquitous terpene cyclases that, instead, assemble terpenes via intramolecular rearrangements of a single substrate. 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 -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 magnesium (Mg)-binding motif found in terpene cyclases. We then applied our structural knowledge of DabA and a homologous enzyme from the kainic acid biosynthetic pathway, KabA, to reengineer their isoprene donor specificities (geranyl diphosphate [GPP] versus dimethylallyl diphosphate [DMAPP]) with a single amino acid change. While diatom DabA and seaweed KabA enzymes share a common evolutionary lineage, they are distinct from all other terpene cyclases, suggesting a very distant ancestor to the larger terpene synthase family.

PubMed: 32457155
DOI: 10.1073/pnas.2001325117

実験手法

X-RAY DIFFRACTION (2.1 Å)