Robust structural, kinetic and biophysical characterization of wild-type human ACOD1, selected mutants and their interaction with citraconate.

Authors

Brent Runge, Hande Oktay, Ian J Fucci, Eric M Merten, Sergey G Tarasov, Lixin Fan, Diana C F Monteiro

Published in

Journal of structural biology: X. Volume 14. Pages 100157. Epub Aug 08, 2026.

Abstract

Aconitate decarboxylase 1, an enzyme member of the MmgE-PrpD family of proteins, has gained significant attention in the last decade as a therapeutic target for cancer and inflammatory diseases. Its product, itaconate, is a multifunctional metabolite shown to drive several disease states. Though extensively studied in cellulo and in vivo, this protein is biochemically and mechanistically under characterized and although a family of inhibitors has been described, no ligand-bound structures have yet been determined. In this work we present a thorough structural investigation that yielded the first ligand-bound structure of this protein family, which required the generation of artifact-free apo crystals. We also developed a novel, low-consumption, robust kinetic assay and investigated active site and allosteric mutants to further elucidate structural and dynamic activity relationships of this protein.

PMID:
42631184
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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