9icz

C-Methyltransferase SeMT from Saccharopolyspora erythraea

spinqualitylabelsall models 9icz, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9icz is a 2 chain structure with sequence from Saccharopolyspora erythraea. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.58Å Ligands: SAH, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A4FFC0_SACEN Publication Abstract from PubMed The pyrroloindole (hexahydropyrrolo[2,3-b]indole, HPI) structural motif is present in a wide range of natural products with various biological activities, yet its chemical synthesis poses a challenge, particularly regarding methylation at the indole C3 position. In nature, S-adenosyl methionine (SAM)-dependent methyltransferases efficiently catalyze this reaction with high stereoselectivity. This study presents the investigation and rational re-design of a potential methyltransferase, termed SeMT, from the actinomycete Saccharopolyspora erythraea. While its three-dimensional structure elucidated via X-ray crystallography confirmed extensive structural similarity to cyclic dipeptide-processing methyltransferases such as SgMT, its putative catalytic center is clearly divergent. Accordingly, wild-type SeMT displayed minimal activity with diketopiperazine (DKP) substrates, triggering an extensive mutagenesis effort aimed at iteratively enhancing this methyltransferase function. This work yielded a variant with appreciable activity, which was comprehensively characterized. Notably, a specific mutation within the catalytic triad of SeMT proved critical not only for its own function but also for the temperature-activity profile of its homolog protein SgMT. Beyond the specific properties of SeMT, these findings hence provide important insights into the active center architecture of indole C3-methyltransferases, supporting further development of these enzymes into refined biocatalysts for synthetic applications. Re-engineering a transferase scaffold for indole C3 methylation in diketopiperazines.,Haase M, Weiergraber OH, Pietruszka J Protein Sci. 2025 Sep;34(9):e70254. doi: 10.1002/pro.70254. PMID:40878043 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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