{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gatreddi S"],"funding":["NIGMS NIH HHS"],"pagination":["2857-2866"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11851776"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(4)"],"pubmed_abstract":["The LarA family consists of diverse racemases/epimerases that interconvert the diastereomers 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 various 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 <i>Isosphaera pallida</i> (LarA <i><sub>Ip</sub></i> ). The substrate binding mode reveals a near-optimal orientation and distance between the hydride donor and acceptor, consistent with an updated proton-coupled hydride transfer mechanism. The experimentally solve"],"journal":["ACS catalysis"],"pubmed_title":["Structural Basis for the Catalysis and Substrate Specificity of a LarA Racemase with a Broad Substrate Spectrum."],"pmcid":["PMC11851776"],"funding_grant_id":["R35 GM140931","R01 GM128959"],"pubmed_authors":["Desguin B","Hu J","Urdiain-Arraiza J","Hausinger RP","Gatreddi S"],"additional_accession":[]},"is_claimable":false,"name":"Structural Basis for the Catalysis and Substrate Specificity of a LarA Racemase with a Broad Substrate Spectrum.","description":"The LarA family consists of diverse racemases/epimerases that interconvert the diastereomers 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 various 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 <i>Isosphaera pallida</i> (LarA <i><sub>Ip</sub></i> ). The substrate binding mode reveals a near-optimal orientation and distance between the hydride donor and acceptor, consistent with an updated proton-coupled hydride transfer mechanism. The experimentally solve","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-02T19:15:33.099Z","creation":"2025-04-04T02:47:48.048Z"},"accession":"S-EPMC11851776","cross_references":{"pubmed":["40013250"],"doi":["10.1021/acscatal.4c07804"]}}