9E56

TAD from Carmabin Biosynthetic Pathway with Disulfide between Cys2238 and Dephosphocoenzyme A - Crystal Form 2

9E56 の概要

• エントリーDOI: 10.2210/pdb9e56/pdb
• 関連するPDBエントリー: 9E4S 9E4U 9E4X 9E50
• 分子名称: Amino acid adenylation domain protein, DEPHOSPHO COENZYME A, IODIDE ION, ... (4 entities in total)
• 機能のキーワード: nad-binding, biosynthetic protein
• 由来する生物種: Moorena producens 3L
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 90530.79

構造登録者

Rankin, M.R.,Smith, J.L. (登録日: 2024-10-27, 公開日: 2025-02-26, 最終更新日: 2025-05-14)

主引用文献

Rankin, M.R.,Khare, D.,Gerwick, L.,Sherman, D.H.,Gerwick, W.H.,Smith, J.L.
Structure of a putative terminal amidation domain in natural product biosynthesis.
Structure, 33:935-, 2025

PubMed Abstract: Bacteria are rich sources of pharmaceutically valuable natural products, many crafted by modular polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). PKS and NRPS systems typically contain a thioesterase (TE) to offload a linear or cyclized product from a carrier protein, but alternative chemistry is needed for products with a terminal amide. Several pathways with amidated products also possess an uncharacterized 400-amino acid terminal domain. We present the characterization and structure of this putative terminal amidation domain (TAD). TAD binds NAD with the nicotinamide near an invariant cysteine that is also accessible to an intermediate on a carrier protein, indicating a catalytic role. The TAD structure resembles cyanobacterial acyl-ACP reductase (AAR), which binds NADPH near an analogous catalytic cysteine. Bioinformatic analysis reveals that TADs are broadly distributed across bacterial phyla and often occur at the end of terminal NRPS modules, suggesting many amidated products may yet be discovered.

PubMed: 40086440
DOI: 10.1016/j.str.2025.02.005

実験手法

X-RAY DIFFRACTION (1.94 Å)