6O0E

Saxiphilin:STX complex, soaking

Summary for 6O0E

• Entry DOI: 10.2210/pdb6o0e/pdb
• Related: 6O0D
• Descriptor: Saxiphilin, [(3aS,4R,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,9,10-tetrahydro-3H,8H-pyrrolo[1,2-c]purin-4-yl]methyl carbamate (3 entities in total)
• Functional Keywords: saxitoxin, paralytic shellfish poisoning, antitoxin
• Biological source: Lithobates catesbeiana (American bullfrog)
• Total number of polymer chains: 2
• Total formula weight: 189055.18

Authors

Yen, T.J.,Lolicato, M.,Minor, D.L. (deposition date: 2019-02-16, release date: 2019-07-10, Last modification date: 2019-12-04)

Primary citation

Yen, T.J.,Lolicato, M.,Thomas-Tran, R.,Du Bois, J.,Minor Jr., D.L.
Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins.
Sci Adv, 5:eaax2650-eaax2650, 2019

PubMed Abstract: Dinoflagelates and cyanobacteria produce saxitoxin (STX), a lethal bis-guanidinium neurotoxin causing paralytic shellfish poisoning. A number of metazoans have soluble STX-binding proteins that may prevent STX intoxication. However, their STX molecular recognition mechanisms remain unknown. Here, we present structures of saxiphilin (Sxph), a bullfrog high-affinity STX-binding protein, alone and bound to STX. The structures reveal a novel high-affinity STX-binding site built from a "proto-pocket" on a transferrin scaffold that also bears thyroglobulin domain protease inhibitor repeats. Comparison of Sxph and voltage-gated sodium channel STX-binding sites reveals a convergent toxin recognition strategy comprising a largely rigid binding site where acidic side chains and a cation-π interaction engage STX. These studies reveal molecular rules for STX recognition, outline how a toxin-binding site can be built on a naïve scaffold, and open a path to developing protein sensors for environmental STX monitoring and new biologics for STX intoxication mitigation.

PubMed: 31223657
DOI: 10.1126/sciadv.aax2650

Experimental method

X-RAY DIFFRACTION (2.5 Å)