Crystal Structure of Histone Deacetylase 6 Complexed with ( R )-Lipoic Acid, an Essential Cofactor in Central Carbon Metabolism.

ABSTRACT: The enzyme cofactor ( R )-lipoic acid plays a critical role in central carbon metabolism due to its catalytic function in the generation of acetyl-CoA, which links glycolysis with the tricarboxylic acid cycle. This cofactor is also essential for the generation of succinyl CoA within the tricarboxylic acid cycle. However, the biological functions of ( R )-lipoic acid extend beyond metabolism owing to its facile redox chemistry. Most recently, the reduced form of ( R )-lipoic acid, ( R )-dihydrolipoic acid, has been shown to inhibit histone deacetylases (HDACs) with selectivity for the inhibition of HDAC6. Here, we report the 2.4 Å-resolution X-ray crystal structure of the HDAC6-( R )-dihydrolipoic acid complex, and we report a dissociation constant (K

SUBMITTER: Watson PR 

PROVIDER: S-EPMC10441330 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature