Structural Basis for Catalysis and Substrate Specificity of a LarA Racemase with a Broad Substrate Spectrum.

ABSTRACT: The LarA family consists of diverse racemases/epimerases that interconvert the diastereomers of a variety of α-hydroxyacids by using a nickel-pincer nucleotide (NPN) cofactor. The hidden redox reaction catalyzed by the NPN cofactor makes LarA enzymes attractive engineering targets for applications. However, how a LarA enzyme binds its natural substrate and recognizes different α-hydroxyacids has not been elucidated. Here, we report three high-resolution structures of the enzyme-substrate complexes of a broad-spectrum LarA enzyme from Isosphaera pallida (LarA _Ip ). The substrate binding mode reveals an optimal orientation and distance between the hydride donor and acceptor, strongly supporting the proposed proton-coupled hydride transfer mechanism. The experimentall

SUBMITTER: Gatreddi S 

PROVIDER: S-EPMC11623692 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature