6PEU

Structure of YcaO enzyme from Methanocaldococcus jannaschii in complex with peptide

6PEU の概要

• エントリーDOI: 10.2210/pdb6peu/pdb
• 関連するPDBエントリー: 6PE3
• 分子名称: Uncharacterized protein MJ1094, GLY-ARG-LEU-GLY-PHE-TYR-GLY-TYR-ASP-LEU-GLN-ASP, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: ycao, atp, thioamide, methanocaldococcus jannaschii, biosynthetic protein
• 由来する生物種: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 184732.85

構造登録者

Dong, S.-H.,Nair, S.K. (登録日: 2019-06-20, 公開日: 2019-11-06, 最終更新日: 2024-03-06)

主引用文献

Dong, S.H.,Liu, A.,Mahanta, N.,Mitchell, D.A.,Nair, S.K.
Mechanistic Basis for Ribosomal Peptide Backbone Modifications.
Acs Cent.Sci., 5:842-851, 2019

PubMed Abstract: YcaO enzymes are known to catalyze the ATP-dependent formation of azoline heterocycles, thioamides, and (macro)lactamidines on peptide substrates. These enzymes are found in multiple biosynthetic pathways, including those for several different classes of ribosomally synthesized and post-translationally modified peptides (RiPPs). However, there are major knowledge gaps in the mechanistic and structural underpinnings that govern each of the known YcaO-mediated modifications. Here, we present the first structure of any YcaO enzyme bound to its peptide substrate in the active site, specifically that from which is involved in the thioamidation of the α-subunit of methyl-coenzyme M reductase (McrA). The structural data are leveraged to identify and test the residues involved in substrate binding and catalysis by site-directed mutagenesis. We also show that thioamide-forming YcaOs can carry out the cyclodehydration of a related peptide substrate, which underscores the mechanistic conservation across the YcaO family and allows for the extrapolation of mechanistic details to azoline-forming YcaOs involved in RiPP biosynthesis. A bioinformatic survey of all YcaOs highlights the diverse sequence space in azoline-forming YcaOs and suggests their early divergence from a common ancestor. The data presented within provide a detailed molecular framework for understanding this family of enzymes, which reconcile several decades of prior data on RiPP cyclodehydratases. These studies also provide the foundational knowledge to impact our mechanistic understanding of additional RiPP biosynthetic classes.

PubMed: 31139720
DOI: 10.1021/acscentsci.9b00124

実験手法

X-RAY DIFFRACTION (1.95 Å)