9Y92

Nanorana parkeri saxiphilin:STX-C13-OBz (co-crystal)

This is a non-PDB format compatible entry.

Summary for 9Y92

• Entry DOI: 10.2210/pdb9y92/pdb
• Descriptor: Saxiphilin, PENTAETHYLENE GLYCOL, [(2Z,3aS,4R,6Z,7R,10aS)-10,10-dihydroxy-2,6-diiminooctahydro-1H,8H-pyrrolo[1,2-c]purin-4-yl]methyl benzoate, ... (4 entities in total)
• Functional Keywords: saxiphilin, toxin resistance, saxitoxin, antitoxin
• Biological source: Nanorana parkeri
• Total number of polymer chains: 1
• Total formula weight: 95302.29

Authors

Zakrzewska, S.,Minor, D.L. (deposition date: 2025-09-12, release date: 2026-05-27, Last modification date: 2026-07-08)

Primary citation

Zakrzewska, S.,Chen, Z.,Park, E.R.,Bhaskar, R.G.,Bedell, T.A.,Du Bois, J.,Minor Jr., D.L.
Saxiphilin is a broad-spectrum toxin sponge for C13-modified saxitoxins.
Structure, 2026

PubMed Abstract: Saxitoxin (STX) and its congeners (paralytic shellfish toxins, PSTs) are among the most potent small-molecule toxins. PSTs are produced by harmful algal blooms and derive toxicity by disrupting voltage-gated sodium channel (Na) bioelectrical signaling. Understanding how PST structural variation affects target binding is crucial for toxin countermeasure development and exploitation of PSTs as drug development leads. Frog and toad saxiphilins (Sxphs) are soluble, high-affinity STX toxin sponges that offer a powerful platform to define PST-protein interactions. Here, we show that American bullfrog (Rana catesbeiana) RcSxph and High Himalaya frog (Nanorana parkeri) NpSxph bind a broad set of C13-modified STX congeners. High-resolution structures unveil "compact" and "open" C13-aryl congener binding modes that depend on the RcSxph Tyr558 environment, highlighting a remarkable adaptability of Sxphs to bind STX analogs and unexpected toxin conformational plasticity. These findings have implications for understanding PST interactions with biological targets and informing design of Na probes and modulators.

PubMed: 42309055
DOI: 10.1016/j.str.2026.05.008

Experimental method

X-RAY DIFFRACTION (1.9 Å)