8V66

Nanorana parkeri saxiphilin:GTX5 (co-crystal)

Summary for 8V66

• Entry DOI: 10.2210/pdb8v66/pdb
• Related: 8V65 8V67 8V68 8V69
• Descriptor: Saxiphilin, PENTAETHYLENE GLYCOL, ({[(3aS,4R,7S,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,9,10-tetrahydro-1H,8H-pyrrolo[1,2-c]purin-4-yl]methoxy}carbonyl)sulfamic acid, ... (4 entities in total)
• Functional Keywords: saxiphilin, toxin resistance, saxitoxin, antitoxin
• Biological source: Nanorana parkeri
• Total number of polymer chains: 1
• Total formula weight: 95321.27

Authors

Zakrzewska, S.,Minor, D.L. (deposition date: 2023-12-01, release date: 2025-05-07)

Primary citation

Zakrzewska, S.,Nixon, S.A.,Chen, Z.,Hajare, H.S.,Park, E.R.,Mulcahy, J.V.,Arlinghaus, K.M.,Neu, E.,Konovalov, K.,Provasi, D.,Leighfield, T.A.,Filizola, M.,Du Bois, J.,Minor Jr., D.L.
Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins.
Nat Commun, 16:3885-3885, 2025

PubMed Abstract: Dinoflagellates and cyanobacteria produce saxitoxin (STX) and ~50 congeners that disrupt bioelectrical signals by blocking voltage-gated sodium channels (Nas). Consuming seafood carrying these toxins causes paralytic shellfish poisoning (PSP). Although Nas and anuran STX binding proteins (saxiphilins, Sxphs) use convergent STX binding modes, the structural basis for STX congener recognition is unknown. Here, we show that American bullfrog (Rana catesbeiana) RcSxph and High Himalaya frog (Nanorana parkeri) NpSxph sequester STX congeners using a 'lock and key' mode shared with STX. Importantly, functional studies demonstrate that Sxph 'toxin sponges' reverse Na block by multiple STX congeners and detect these toxins in a radioligand binding assay (RBA) used for environmental testing. Together, our study establishes how Sxphs sequester select neurotoxins and uncover STX congener-specific interactions distinct from Nas. These findings expand understanding of toxin sponge action and provide a foundation for strategies to monitor and mitigate the harmful effects of STX congeners.

PubMed: 40274765
DOI: 10.1038/s41467-025-58903-2

Experimental method

X-RAY DIFFRACTION (1.9 Å)