6ryz
From Proteopedia
SalL with S-adenosyl methionine
Structural highlights
FunctionSALL_SALTO Involved in the biosynthesis of the proteosome inhibitor salinosporamide A (SalA). Catalyzes the halogenation of S-adenosyl-L-methionine (SAM) with chloride to generate 5'-chloro-5'-deoxyadenosine (5'-CIDA) and L-methionine. It can also use bromide and iodide, producing halogenated 5'-deoxyadenosine (5'-XDA) and L-methionine, however no halogenase activity is detected in the presence of fluoride.[1] Publication Abstract from PubMedA tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5'-chloro-5'-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants that influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules. S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation.,McKean IJW, Sadler JC, Cuetos A, Frese A, Humphreys LD, Grogan G, Hoskisson PA, Burley GA Angew Chem Int Ed Engl. 2019 Dec 2;58(49):17583-17588. doi:, 10.1002/anie.201908681. Epub 2019 Oct 21. PMID:31573135[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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