Snapshots From the Catalytic Landscape of Chalcone Isomerase.
- 1Department of Chemistry and Biochemistry California State University San Bernardino San Bernardino California USA.
Abstract
Chalcone isomerase (CHI) catalyzes the cyclization of three-ring scaffolds of flavonoids, a class of plant-based natural products important for nutrition and disease prevention. A persistent question has been whether the enzyme uses protein dynamics to facilitate conformational rearrangements of substrates within the active site. To help resolve this question, CHI from Medicago truncatula was crystallized with phloretin, a flexible substrate analogue that cannot undergo cyclization, and solved to 2.0-Å resolution. The crystal structure possesses eight protein molecules per asymmetric unit, revealing different active site conformations that accommodate different bound conformers of phloretin. Together, the structural snapshots depict a series of coordinated, dynamic chemical interactions that lower barriers to substrate rearrangements approaching bond formation. Differential scanning fluorimetry combined with mutational analysis and enzyme kinetics further confirms that phloretin binds to the enzyme active site, and that it acts as a competitive inhibitor of CHI. Together, these findings answer outstanding questions about the flexibility and dynamics of CHI catalysis, information that may be useful for future biosynthetic design and enzyme engineering goals. Overall, this work supports a catalytic model in which the CHI enzyme operates as a dynamic ensemble of structures necessary to facilitate catalytic substrate rearrangements.
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BibTeX
@article{burke2026snapshots,
title = {{Snapshots From the Catalytic Landscape of Chalcone Isomerase.}},
author = {Jason R Burke and Matthew A Rangel and Vanessa I Vasquez Meza and Hailey N Mims and Thomas O Darko and Kelwyn Ixcoy and Alfredo Ruiz Rivera and Jason Zhang and Emma R Wolf-Saxon and Chad C Moorman},
journal = {Plant direct},
year = {2026},
month = oct,
doi = {10.1002/pld3.70200},
url = {https://europepmc.org/article/MED/42890497},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Snapshots From the Catalytic Landscape of Chalcone Isomerase.
AU - Jason R Burke
AU - Matthew A Rangel
AU - Vanessa I Vasquez Meza
AU - Hailey N Mims
AU - Thomas O Darko
AU - Kelwyn Ixcoy
AU - Alfredo Ruiz Rivera
AU - Jason Zhang
AU - Emma R Wolf-Saxon
AU - Chad C Moorman
PY - 2026
DA - 2026/10/16
JO - Plant direct
DO - 10.1002/pld3.70200
UR - https://europepmc.org/article/MED/42890497
AB - Chalcone isomerase (CHI) catalyzes the cyclization of three-ring scaffolds of flavonoids, a class of plant-based natural products important for nutrition and disease prevention. A persistent question has been whether the enzyme uses protein dynamics to facilitate conformational rearrangements of substrates within the active site. To help resolve this question, CHI from Medicago truncatula was crystallized with phloretin, a flexible substrate analogue that cannot undergo cyclization, and solved to 2.0-Å resolution. The crystal structure possesses eight protein molecules per asymmetric unit, revealing different active site conformations that accommodate different bound conformers of phloretin. Together, the structural snapshots depict a series of coordinated, dynamic chemical interactions that lower barriers to substrate rearrangements approaching bond formation. Differential scanning fluorimetry combined with mutational analysis and enzyme kinetics further confirms that phloretin binds to the enzyme active site, and that it acts as a competitive inhibitor of CHI. Together, these findings answer outstanding questions about the flexibility and dynamics of CHI catalysis, information that may be useful for future biosynthetic design and enzyme engineering goals. Overall, this work supports a catalytic model in which the CHI enzyme operates as a dynamic ensemble of structures necessary to facilitate catalytic substrate rearrangements.
SN - 2475-4455
ER -