8V2V

Solution NMR structure of recifin A [Y6F]

8V2V の概要

• エントリーDOI: 10.2210/pdb8v2v/pdb
• NMR情報: BMRB: 31130
• 分子名称: Recifin A, PYROGLUTAMIC ACID (2 entities in total)
• 機能のキーワード: cystine-rich peptide, protein knot, tyrosyl-dna phosphodiesterase i inhibitor, marine natural product, toxin
• 由来する生物種: Axinella sp. 1 TF-2017
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4926.46

構造登録者

Payne, C.D.,Schroeder, C.I.,Rosengren, K.J. (登録日: 2023-11-23, 公開日: 2024-09-25)

主引用文献

Smallwood, T.B.,Krumpe, L.R.H.,Payne, C.D.,Klein, V.G.,O'Keefe, B.R.,Clark, R.J.,Schroeder, C.I.,Rosengren, K.J.
Picking the tyrosine-lock: chemical synthesis of the tyrosyl-DNA phosphodiesterase I inhibitor recifin A and analogues.
Chem Sci, 15:13227-13233, 2024

PubMed Abstract: The peptide recifin A is the inaugural member of the structurally intriguing new fold referred to as a tyrosine-lock. Its central four stranded β-sheet is stabilized by a unique arrangement in which three disulfide bonds and their interconnecting backbone form a ring that wraps around one of the strands, resulting in a Tyr side chain being buried in the molecular core. Here we aimed to establish a synthetic route to this complex class of natural products. Full length recifin A was successfully generated through native chemical ligation chemistry joining two 21 amino acid residue fragments. Surprisingly, reduced linear recifin A readily adopts the correct, topologically-complex fold random oxidation of the cysteines, suggesting it is highly energetically favored. Utilizing our synthetic strategy, we generated five recifin A analogues to investigate the structural role of the central Tyr residue and provide the first insights into the structure activity relationship of recifin A towards its cancer target tyrosyl-DNA phosphodiesterase I.

PubMed: 39183914
DOI: 10.1039/d4sc01976h

実験手法

SOLUTION NMR