8d6t

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8d6t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lithobates_catesbeianus Lithobates catesbeianus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8D6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D6T FirstGlance]. <br>
<table><tr><td colspan='2'>[[8d6t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lithobates_catesbeianus Lithobates catesbeianus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8D6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D6T FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SL:[(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'>9SL</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SL:[(3~{a}~{S},4~{R},10~{a}~{S})-2,6-bis(azanyl)-10,10-bis(oxidanyl)-3~{a},4,8,9-tetrahydro-3~{H}-pyrrolo[1,2-c]purin-4-yl]methyl+carbamate'>9SL</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8d6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d6t OCA], [https://pdbe.org/8d6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d6t RCSB], [https://www.ebi.ac.uk/pdbsum/8d6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d6t ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8d6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d6t OCA], [https://pdbe.org/8d6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d6t RCSB], [https://www.ebi.ac.uk/pdbsum/8d6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d6t ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/SAX_LITCT SAX_LITCT] 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.
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[https://www.uniprot.org/uniprot/SAX_AQUCT SAX_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.
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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American bullfrog (Rana castesbeiana) saxiphilin (RcSxph) is a high-affinity "toxin sponge" protein thought to prevent intoxication by saxitoxin (STX), a lethal bis-guanidinium neurotoxin that causes paralytic shellfish poisoning (PSP) by blocking voltage-gated sodium channels (NaVs). How specific RcSxph interactions contribute to STX binding has not been defined and whether other organisms have similar proteins is unclear. Here, we use mutagenesis, ligand binding, and structural studies to define the energetic basis of Sxph:STX recognition. The resultant STX "recognition code" enabled engineering of RcSxph to improve its ability to rescue NaVs from STX and facilitated discovery of 10 new frog and toad Sxphs. Definition of the STX binding code and Sxph family expansion among diverse anurans separated by approximately 140 My of evolution provides a molecular basis for understanding the roles of toxin sponge proteins in toxin resistance and for developing novel proteins to sense or neutralize STX and related PSP toxins.
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American bullfrog (Rana castesbeiana) saxiphilin (RcSxph) is a high-affinity "toxin sponge" protein thought to prevent intoxication by saxitoxin (STX), a lethal bis-guanidinium neurotoxin that causes paralytic shellfish poisoning (PSP) by blocking voltage-gated sodium channels (Na(V)s). How specific RcSxph interactions contribute to STX binding has not been defined and whether other organisms have similar proteins is unclear. Here, we use mutagenesis, ligand binding, and structural studies to define the energetic basis of Sxph:STX recognition. The resultant STX "recognition code" enabled engineering of RcSxph to improve its ability to rescue Na(V)s from STX and facilitated discovery of 10 new frog and toad Sxphs. Definition of the STX binding code and Sxph family expansion among diverse anurans separated by approximately 140 My of evolution provides a molecular basis for understanding the roles of toxin sponge proteins in toxin resistance and for developing novel proteins to sense or neutralize STX and related PSP toxins.
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Definition of a saxitoxin (STX) binding code enables discovery and characterization of the anuran saxiphilin family.,Chen Z, Zakrzewska S, Hajare HS, Alvarez-Buylla A, Abderemane-Ali F, Bogan M, Ramirez D, O'Connell LA, Du Bois J, Minor DL Jr Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2210114119. doi:, 10.1073/pnas.2210114119. Epub 2022 Oct 24. PMID:36279441<ref>PMID:36279441</ref>
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Definition of a saxitoxin (STX) binding code enables discovery and characterization of the anuran saxiphilin family.,Chen Z, Zakrzewska S, Hajare HS, Alvarez-Buylla A, Abderemane-Ali F, Bogan M, Ramirez D, O'Connell LA, Du Bois J, Minor DL Jr Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2210114119. doi: , 10.1073/pnas.2210114119. Epub 2022 Oct 24. PMID:36279441<ref>PMID:36279441</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Current revision

Rana catesbeiana saxiphilin mutant - Y558I:STX (co-crystal)

PDB ID 8d6t

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