8A74

PcIDS1_F315A in complex with Mg2+ and GPP

Summary for 8A74

• Entry DOI: 10.2210/pdb8a74/pdb
• Related: 8A6U
• Descriptor: Isoprenyl diphosphate synthase, MAGNESIUM ION, GERANYL DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: insects, biosynthesis, terpenes, metal regulation, catalysis, biosynthetic protein
• Biological source: Phaedon cochleariae (mustard beetle)
• Total number of polymer chains: 2
• Total formula weight: 80628.59

Authors

Ecker, F.,Boland, W.,Groll, M. (deposition date: 2022-06-20, release date: 2023-05-31, Last modification date: 2024-02-07)

Primary citation

Ecker, F.,Vattekkatte, A.,Boland, W.,Groll, M.
Metal-dependent enzyme symmetry guides the biosynthetic flux of terpene precursors.
Nat.Chem., 15:1188-1195, 2023

PubMed Abstract: Terpenoids account for more than 60% of all natural products, and their carbon skeletons originate from common isoprenoid units of different lengths such as geranyl pyrophosphate and farnesyl pyrophosphate. Here we characterize a metal-dependent, bifunctional isoprenyl diphosphate synthase from the leaf beetle Phaedon cochleariae by structural and functional analyses. Inter- and intramolecular cooperative effects in the homodimer strongly depend on the provided metal ions and regulate the biosynthetic flux of terpene precursors to either biological defence or physiological development. Strikingly, a unique chain length determination domain adapts to form geranyl or farnesyl pyrophosphate by altering enzyme symmetry and ligand affinity between both subunits. In addition, we identify an allosteric geranyl-pyrophosphate-specific binding site that shares similarity with end-product inhibition in human farnesyl pyrophosphate synthase. Our combined findings elucidate a deeply intertwined reaction mechanism in the P. cochleariae isoprenyl diphosphate synthase that integrates substrate, product and metal-ion concentrations to harness its dynamic potential.

PubMed: 37308711
DOI: 10.1038/s41557-023-01235-9

Experimental method

X-RAY DIFFRACTION (1.9 Å)