8UKG

Solution NMR structure of the lasso peptide wygwalassin-A1

8UKG の概要

• エントリーDOI: 10.2210/pdb8ukg/pdb
• NMR情報: BMRB: 31110
• 分子名称: Lassopeptide wygwalassin-A1 (1 entity in total)
• 機能のキーワード: lassopeptide, unknown function
• 由来する生物種: Streptomyces katrae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1705.82

構造登録者

Saad, H.,Zhu, L.,Harris, L.A.,Shelton, K.E.,Mitchell, D.A. (登録日: 2023-10-13, 公開日: 2024-09-25)

主引用文献

Harris, L.A.,Saad, H.,Shelton, K.E.,Zhu, L.,Guo, X.,Mitchell, D.A.
Tryptophan-Centric Bioinformatics Identifies New Lasso Peptide Modifications.
Biochemistry, 63:865-879, 2024

PubMed Abstract: Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) defined by a macrolactam linkage between the N-terminus and the side chain of an internal aspartic acid or glutamic acid residue. Instead of adopting a branched-cyclic conformation, lasso peptides are "threaded", with the C-terminal tail passing through the macrocycle to present a kinetically trapped rotaxane conformation. The availability of enhanced bioinformatics methods has led to a significant increase in the number of secondary modifications found on lasso peptides. To uncover new ancillary modifications in a targeted manner, a bioinformatic strategy was developed to discover lasso peptides with modifications to tryptophan. This effort identified numerous putative lasso peptide biosynthetic gene clusters with core regions of the precursor peptides enriched in tryptophan. Parsing of these tryptophan (Trp)-rich biosynthetic gene clusters uncovered several putative ancillary modifying enzymes, including halogenases and dimethylallyltransferases expected to act upon Trp. Characterization of two gene products yielded a lasso peptide with two 5-Cl-Trp modifications (chlorolassin) and another bearing 5-dimethylallyl-Trp and 2,3-didehydro-Tyr modifications (wygwalassin). Bioinformatic analysis of the requisite halogenase and dimethylallyltransferase revealed numerous other putative Trp-modified lasso peptides that remain uncharacterized. We anticipate that the Trp-centric strategy reported herein may be useful in discovering ancillary modifications for other RiPP classes and, more generally, guide the functional prediction of enzymes that act on specific amino acids.

PubMed: 38498885
DOI: 10.1021/acs.biochem.4c00035

実験手法

SOLUTION NMR