Abstract
Streptosporangium sibiricum SibL catalyzes the methyl transfer from S-adenosylmethionine (SAM) to 3-hydroxykynurenine (3-HK) to produce S-adenosylhomocysteine (SAH) and 3-hydroxy-4-methyl-kynurenine for sibiromycin biosynthesis. Here, we present the crystal structures of apo-form Ss-SibL, Ss-SibL/SAH binary complex and Ss-SibL/SAH/3-HK ternary complex. Ss-SibL is a homodimer. Each subunit comprises a helical N-terminal domain and a Rossmann-fold C-terminal domain. SAM (or SAH) binding alone results in domain movements, suggesting a two-step catalytic cycle. Analyses of the enzyme-ligand interactions and further mutant studies support a mechanism in which Tyr134 serves as the principal base in the transferase reaction of methyl group from SAM to 3-HK.
Highlights
Sibiromycin, anthramycin and tomaymycin are PBD derivatives with a pharmacophore consisting of a tricyclic moiety that is biosynthesized by combining l-tryptophan, l-tyrosine, and l-methionine[2,8]
Evidence suggests that the family of natural product methyltransferases (NPMTs) is a result of concomitant gene fusions, which led to neofunctionalization of substrate recognition by new domains[20,21,22,23]
The Ss-SibL/SAH crystals were obtained by using SAM, the methyl group lacked corresponding densities and the ligand could only be modeled as the demethylated product (Fig. 2b)
Summary
Sibiromycin, anthramycin and tomaymycin are PBD derivatives with a pharmacophore consisting of a tricyclic moiety (anthranilate, diazepine, and hydropyrrole) that is biosynthesized by combining l-tryptophan, l-tyrosine, and l-methionine[2,8]. The Ss-SibL/SAH crystals were obtained by using SAM, the methyl group lacked corresponding densities and the ligand could only be modeled as the demethylated product (Fig. 2b).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
