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Structural Insights into Peptide Recognition and Modification by the Radical SAM Enzyme SuiB
Author(s) -
Davis Katherine M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.796.9
Subject(s) - peptide , biosynthesis , enzyme , nonribosomal peptide , chemistry , peptide synthesis , biochemistry , peptide biosynthesis , peptide sequence , active site , stereochemistry , combinatorial chemistry , gene , ribosome , rna
Posttranslational modification of ribosomally synthesized peptides provides an elegant means for the production of biologically active molecules. Unlike nonribosomal peptides, which are assembled by large multimodular enzymes, ribosomally synthesized and posttranslationally modified peptides, or RiPPs, have comparatively simple biosynthetic pathways. Modifications to the core sequence of the precursor peptide are installed by tailoring enzymes, however, the structural basis for substrate recognition in these reactions remains unknown. Using X‐ray crystallography and computational modeling, we examine the role of the N‐terminal leader peptide in the biosynthesis of a streptide homolog, a recently identified peptide natural product with an intramolecular lysine–tryptophan crosslink installed by the radical S ‐adenosylmethionine (SAM) enzyme, SuiB. We evaluate a series of structures that not only help to elucidate the formation of the C–C crosslink but also provide insights into the interplay between RiPP precursor peptides and tailoring enzymes more generally. Surprisingly, although the N‐terminal domain of SuiB adopts a typical RRE (RiPP recognition element) motif, which has been implicated in precursor peptide recognition, we observe binding of the leader peptide in the catalytic barrel. Computational simulations support a mechanism in which the leader peptide guides posttranslational modification by positioning the cross‐linking residues of the precursor peptide within the active site. Together, these findings reveal unanticipated roles for the RRE and other domains during RiPP biosynthesis by radical SAM enzymes. Support or Funding Information This work was supported by the Arnold O. Beckman Postdoctoral Fellowship program. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .