8A7R

PcIDS1_I420A in complex with Mg2+ and GPP

PDB DOI: https://doi.org/10.2210/pdb8A7R/pdb

Classification: BIOSYNTHETIC PROTEIN
Organism(s): Phaedon cochleariae
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2022-06-21 Released: 2023-05-31
Deposition Author(s): Ecker, F., Boland, W., Groll, M.
Funding Organization(s): German Research Foundation (DFG)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 ?
R-Value Free: 0.230
R-Value Work: 0.187
R-Value Observed: 0.189

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Metal-dependent enzyme symmetry guides the biosynthetic flux of terpene precursors.

Ecker, F., Vattekkatte, A., Boland, W., Groll, M.

(2023) Nat Chem 15: 1188-1195

PubMed: 37308711 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41557-023-01235-9
Primary Citation of Related Structures:
8A6U, 8A6V, 8A6Z, 8A70, 8A73, 8A74, 8A78, 8A7A, 8A7B, 8A7C, 8A7J, 8A7K, 8A7L, 8A7R, 8A7U

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.

Organizational Affiliation

Center for Protein Assemblies, Technical University of Munich, Garching, Germany.

Macromolecule Content

Total Structure Weight: 80.57 kDa
Atom Count: 5,484
Modelled Residue Count: 653
Deposited Residue Count: 692
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Isoprenyl diphosphate synthase	A, B	346	Phaedon cochleariae	Mutation(s): 1 EC: 2.5.1.1
UniProt
Find proteins for M1JS91 (Phaedon cochleariae) Explore M1JS91 Go to UniProtKB: M1JS91
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	M1JS91
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
GPP (Subject of Investigation/LOI) Query on GPP Download Ideal Coordinates CCD File SDF format, chain G [auth A] MOL2 format, chain G [auth A] mmCIF format, chain G [auth A]	G [auth A]	GERANYL DIPHOSPHATE C₁₀ H₂₀ O₇ P₂ GVVPGTZRZFNKDS-JXMROGBWSA-N		Interactions Focus chain G [auth A] Interactions & Density Focus chain G [auth A]
MES (Subject of Investigation/LOI) Query on MES Download Ideal Coordinates CCD File SDF format, chain F [auth A] MOL2 format, chain F [auth A] mmCIF format, chain F [auth A]	F [auth A]	2-(N-MORPHOLINO)-ETHANESULFONIC ACID C₆ H₁₃ N O₄ S SXGZJKUKBWWHRA-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain I [auth B] MOL2 format, chain I [auth B] mmCIF format, chain I [auth B]	I [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain I [auth B] Interactions & Density Focus chain I [auth B]
MG (Subject of Investigation/LOI) Query on MG Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain H [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B]	C [auth A], D [auth A], E [auth A], H [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B]