7JS6

Solution NMR structure of des-citrulassin F

Summary for 7JS6

• Entry DOI: 10.2210/pdb7js6/pdb
• NMR Information: BMRB: 30787
• Descriptor: des-citrulassin F (1 entity in total)
• Functional Keywords: lasso peptide, ripp, unknown function, citrulline
• Biological source: Streptomyces avermitilis
• Total number of polymer chains: 1
• Total formula weight: 1658.92

Authors

Harris, L.A.,Mitchell, D.A. (deposition date: 2020-08-13, release date: 2020-12-16, Last modification date: 2024-10-30)

Primary citation

Harris, L.A.,Saint-Vincent, P.M.B.,Guo, X.,Hudson, G.A.,DiCaprio, A.J.,Zhu, L.,Mitchell, D.A.
Reactivity-Based Screening for Citrulline-Containing Natural Products Reveals a Family of Bacterial Peptidyl Arginine Deiminases.
Acs Chem.Biol., 15:3167-3175, 2020

PubMed Abstract: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a family of natural products defined by a genetically encoded precursor peptide that is processed by associated biosynthetic enzymes to form the mature product. Lasso peptides are a class of RiPP defined by an isopeptide linkage between the N-terminal amine and an internal Asp/Glu residue with the C-terminal sequence threaded through the macrocycle. This unique lariat topology, which typically provides considerable stability toward heat and proteases, has stimulated interest in lasso peptides as potential therapeutics. Post-translational modifications beyond the class-defining, threaded macrolactam have been reported, including one example of Arg deimination to yield citrulline (Cit). Although a Cit-containing lasso peptide (i.e., citrulassin) was serendipitously discovered during a genome-guided campaign, the gene(s) responsible for Arg deimination has remained unknown. Herein, we describe the use of reactivity-based screening to discriminate bacterial strains that produce Arg- versus Cit-bearing citrulassins, yielding 13 new lasso peptide variants. Partial phylogenetic profiling identified a distally encoded peptidyl arginine deiminase (PAD) gene ubiquitous to the Cit-containing variants. Absence of this gene correlated strongly with lasso peptide variants only containing Arg (i.e., -citrulassin). Heterologous expression of the PAD gene in a -citrulassin producer resulted in the production of the deiminated analog, confirming PAD involvement in Arg deimination. The PADs were then bioinformatically surveyed to provide a deeper understanding of their taxonomic distribution and genomic contexts and to facilitate future studies that will evaluate any additional biochemical roles for the superfamily.

PubMed: 33249828
DOI: 10.1021/acschembio.0c00685

Experimental method

SOLUTION NMR