8V2V
Solution NMR structure of recifin A [Y6F]
Summary for 8V2V
| Entry DOI | 10.2210/pdb8v2v/pdb |
| NMR Information | BMRB: 31130 |
| Descriptor | Recifin A, PYROGLUTAMIC ACID (2 entities in total) |
| Functional Keywords | cystine-rich peptide, protein knot, tyrosyl-dna phosphodiesterase i inhibitor, marine natural product, toxin |
| Biological source | Axinella sp. 1 TF-2017 |
| Total number of polymer chains | 1 |
| Total formula weight | 4926.46 |
| Authors | |
| Primary citation | 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 Cited by 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: 39183914DOI: 10.1039/d4sc01976h PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
