6o0f
Saxiphilin:STX complex, co-crystal
Structural highlights
FunctionSAX_AQUCT Binds specifically to the neurotoxin saxitoxin. Its physiological role may be to transport or sequester an endogenous organic molecule other than Fe(3+). It may participate in a detoxification mechanism for neutralizing a microbial toxin. Publication Abstract from PubMedDinoflagelates 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-pi interaction engage STX. These studies reveal molecular rules for STX recognition, outline how a toxin-binding site can be built on a naive scaffold, and open a path to developing protein sensors for environmental STX monitoring and new biologics for STX intoxication mitigation. Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins.,Yen TJ, Lolicato M, Thomas-Tran R, Du Bois J, Minor DL Jr Sci Adv. 2019 Jun 19;5(6):eaax2650. doi: 10.1126/sciadv.aax2650. eCollection 2019, Jun. PMID:31223657[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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