Analysis of apo and citraconate-bound hACOD1 (hIRG1) by X-ray crystallography and NMR spectroscopy: Structural insights for developing chemotherapeutic agents.

ABSTRACT: In this work, we present the high-resolution structure of human aconitate decarboxylase 1 (hACOD1) in its true apo form (active site empty) as well in complex with the inhibitor citraconate. These two new structures show the architecture of the active site and the structure-activity relationships of citraconate inhibition. Careful analysis of the structures indicates probable dynamics required for substrate/inhibitor binding and catalysis. These observations were further explored using molecular dynamic simulations, which show a clear open-close mechanism of hACOD1 between the A1 and A2 loops, the lid- and helical-domain respectively. As part of the biochemical characterization of the protein, we also developed an alternative kinetic assay which measures the rate of catalysis of hACOD1 by

SUBMITTER: Runge B 

PROVIDER: S-EPMC12259180 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature