This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2mun

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Solution structure of mu-SLPTX3-Ssm6a

Structural highlights

2mun is a 1 chain structure with sequence from Scolopendra subspinipes. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TX32A_SCOMU Gating-modifier toxin that inhibits voltage-gated sodium channel with a preference for hNav1.7/SCN9A (IC(50)=25.4 nM) over hNav1.1/SCN1A (IC(50)=4.1 uM), hNav1.2/SCN2A (IC(50)=813 nM), and hNav1.6/SCN8A (IC(50)=15.2 uM) (PubMed:24082113). Is an effective analgesic in rodent pain models, since it is several-fold more effective than morphine in a rodent model of formalin-induced pain and is equipotent with morphine in its ability to reduce thermal and acid-induced pain (PubMed:24082113). In addition, this peptide shows a high level of resistance to proteases and a high thermal stability that may be explained by its predominant composition of alpha-helices (PubMed:24082113).^[1]

Publication Abstract from PubMed

Arthropod venoms consist primarily of peptide toxins that are injected into their prey with devastating consequences. Venom proteins are thought to be recruited from endogenous body proteins and mutated to yield neofunctionalized toxins with remarkable affinity for specific subtypes of ion channels and receptors. However, the evolutionary history of venom peptides remains poorly understood. Here we show that a neuropeptide hormone has been convergently recruited into the venom of spiders and centipedes and evolved into a highly stable toxin through divergent modification of the ancestral gene. High-resolution structures of representative hormone-derived toxins revealed they possess a unique structure and disulfide framework and that the key structural adaptation in weaponization of the ancestral hormone was loss of a C-terminal alpha helix, an adaptation that occurred independently in spiders and centipedes. Our results raise a new paradigm for toxin evolution and highlight the value of structural information in providing insight into protein evolution.

Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators.,Undheim EA, Grimm LL, Low CF, Morgenstern D, Herzig V, Zobel-Thropp P, Pineda SS, Habib R, Dziemborowicz S, Fry BG, Nicholson GM, Binford GJ, Mobli M, King GF Structure. 2015 Jun 2. pii: S0969-2126(15)00181-1. doi:, 10.1016/j.str.2015.05.003. PMID:26073605^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yang S, Xiao Y, Kang D, Liu J, Li Y, Undheim EA, Klint JK, Rong M, Lai R, King GF. Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17534-9. doi:, 10.1073/pnas.1306285110. Epub 2013 Sep 30. PMID:24082113 doi:http://dx.doi.org/10.1073/pnas.1306285110
↑ Undheim EA, Grimm LL, Low CF, Morgenstern D, Herzig V, Zobel-Thropp P, Pineda SS, Habib R, Dziemborowicz S, Fry BG, Nicholson GM, Binford GJ, Mobli M, King GF. Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators. Structure. 2015 Jun 2. pii: S0969-2126(15)00181-1. doi:, 10.1016/j.str.2015.05.003. PMID:26073605 doi:http://dx.doi.org/10.1016/j.str.2015.05.003

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2mun"

Categories: Large Structures | Scolopendra subspinipes | King GF | Mobli M | Undheim EAB

@@ Line 1: / Line 1: @@
 ==Solution structure of mu-SLPTX3-Ssm6a==
-<StructureSection load='2mun' size='340' side='right'caption='[[2mun]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
+<StructureSection load='2mun' size='340' side='right'caption='[[2mun]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Chinese_red-headed_centipede Chinese red-headed centipede]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MUN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Scolopendra_subspinipes Scolopendra subspinipes]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MUN FirstGlance]. <br>
 </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=2mun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mun OCA], [https://pdbe.org/2mun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mun RCSB], [https://www.ebi.ac.uk/pdbsum/2mun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mun ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/TX32A_SCOMU TX32A_SCOMU] Gating-modifier toxin that inhibits voltage-gated sodium channel with a preference for hNav1.7/SCN9A (IC(50)=25.4 nM) over hNav1.1/SCN1A (IC(50)=4.1 uM), hNav1.2/SCN2A (IC(50)=813 nM), and hNav1.6/SCN8A (IC(50)=15.2 uM) (PubMed:24082113). Is an effective analgesic in rodent pain models, since it is several-fold more effective than morphine in a rodent model of formalin-induced pain and is equipotent with morphine in its ability to reduce thermal and acid-induced pain (PubMed:24082113). In addition, this peptide shows a high level of resistance to proteases and a high thermal stability that may be explained by its predominant composition of alpha-helices (PubMed:24082113).<ref>PMID:24082113</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 21: @@
 __TOC__
 </StructureSection>
-[[Category: Chinese red-headed centipede]]
 [[Category: Large Structures]]
-[[Category: King, G F]]
+[[Category: Scolopendra subspinipes]]
-[[Category: Mobli, M]]
+[[Category: King GF]]
-[[Category: Undheim, E A.B]]
+[[Category: Mobli M]]
-[[Category: Crustacean hyperglycemic hormone]]
+[[Category: Undheim EAB]]
-[[Category: Ion channel inhibitor]]
-[[Category: Mu-slptx-ssm6a]]
-[[Category: Toxin]]

2mun

From Proteopedia

Current revision

Solution structure of mu-SLPTX3-Ssm6a

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox