3WVR

Structure of ATP grasp protein with AMP

3WVR の概要

• エントリーDOI: 10.2210/pdb3wvr/pdb
• 関連するPDBエントリー: 3WVQ
• 分子名称: PGM1, SULFATE ION, ADENOSINE MONOPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: atp grasp domain, ligase, biosynthetic protein
• 由来する生物種: Streptomyces cirratus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 197231.36

構造登録者

Matsui, T.,Noike, M.,Ooya, K.,Sasaki, I.,Hamano, Y.,Maruyama, C.,Ishikawa, J.,Satoh, Y.,Ito, H.,Dairi, T.,Morita, H. (登録日: 2014-06-04, 公開日: 2014-11-19, 最終更新日: 2024-11-20)

主引用文献

Noike, M.,Matsui, T.,Ooya, K.,Sasaki, I.,Ohtaki, S.,Hamano, Y.,Maruyama, C.,Ishikawa, J.,Satoh, Y.,Ito, H.,Morita, H.,Dairi, T.
A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin.
Nat.Chem.Biol., 11:71-76, 2015

PubMed Abstract: Peptide antibiotics are typically biosynthesized by one of two distinct machineries in a ribosome-dependent or ribosome-independent manner. Pheganomycin (PGM (1)) and related analogs consist of the nonproteinogenic amino acid (S)-2-(3,5-dihydroxy-4-hydroxymethyl)phenyl-2-guanidinoacetic acid (2) and a proteinogenic core peptide, making their origin uncertain. We report the identification of the biosynthetic gene cluster from Streptomyces cirratus responsible for PGM production. Unexpectedly, the cluster contains a gene encoding multiple precursor peptides along with several genes plausibly encoding enzymes for the synthesis of amino acid 2. We identified PGM1, which has an ATP-grasp domain, as potentially capable of linking the precursor peptides with 2, and validate this hypothesis using deletion mutants and in vitro reconstitution. We document PGM1's substrate permissivity, which could be rationalized by a large binding pocket as confirmed via structural and mutagenesis experiments. This is to our knowledge the first example of cooperative peptide synthesis achieved by ribosomes and peptide ligases using a peptide nucleophile.

PubMed: 25402768
DOI: 10.1038/nchembio.1697

実験手法

X-RAY DIFFRACTION (2.175 Å)