2mun - Revision history

OCA at 09:46, 14 June 2023

OCA — Wed, 14 Jun 2023 09:46:59 GMT

←Older revision		Revision as of 09:46, 14 June 2023
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	==Solution structure of mu-SLPTX3-Ssm6a==		==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 ==		== 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>		</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>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Chinese red-headed centipede]]
	[[Category: Large Structures]]		[[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~~]]	+

OCA at 09:03, 23 February 2022

OCA — Wed, 23 Feb 2022 09:03:27 GMT

←Older revision		Revision as of 09:03, 23 February 2022
Line 3:		Line 3:
	<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]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure with sequence from [~~http~~://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 [~~http~~://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/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>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=2mun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mun OCA], [~~http~~://pdbe.org/2mun PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2mun RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2mun PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2mun ProSAT]</span></td></tr>	+	</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>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 06:28, 20 May 2020

OCA — Wed, 20 May 2020 06:28:39 GMT

←Older revision		Revision as of 06:28, 20 May 2020
Line 1:		Line 1:

	==Solution structure of mu-SLPTX3-Ssm6a==		==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]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure with sequence from [http://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 [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2MUN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure with sequence from [http://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 [http://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'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2mun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mun OCA], [http://pdbe.org/2mun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mun RCSB], [http://www.ebi.ac.uk/pdbsum/2mun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mun ProSAT]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2mun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mun OCA], [http://pdbe.org/2mun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mun RCSB], [http://www.ebi.ac.uk/pdbsum/2mun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mun ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 20:		Line 20:
	</StructureSection>		</StructureSection>
	[[Category: Chinese red-headed centipede]]		[[Category: Chinese red-headed centipede]]
		+	[[Category: Large Structures]]
	[[Category: King, G F]]		[[Category: King, G F]]
	[[Category: Mobli, M]]		[[Category: Mobli, M]]

OCA at 16:57, 15 August 2018

OCA — Wed, 15 Aug 2018 16:57:51 GMT

←Older revision		Revision as of 16:57, 15 August 2018
Line 1:		Line 1:
		+
	==Solution structure of mu-SLPTX3-Ssm6a==		==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]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MUN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mun OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mun RCSB], [http://www.ebi.ac.uk/pdbsum/2mun PDBsum]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mun OCA], [http://pdbe.org/2mun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mun RCSB], [http://www.ebi.ac.uk/pdbsum/2mun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mun ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 13:		Line 14:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2mun" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Chinese red-headed centipede]]
	[[Category: King, G F]]		[[Category: King, G F]]
	[[Category: Mobli, M]]		[[Category: Mobli, M]]

OCA at 07:42, 26 August 2015

OCA — Wed, 26 Aug 2015 07:42:36 GMT

←Older revision		Revision as of 07:42, 26 August 2015
Line 7:		Line 7:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Loss-~~of~~-function mutations in the human voltage-gated sodium channel NaV1.7 result in a congenital indifference to pain. Selective inhibitors of NaV1~~.7 are ~~therefore likely~~ to be ~~powerful analgesics~~ for ~~treating a broad range~~ of ~~pain conditions~~. ~~Herein we describe~~ the ~~identification~~ of ~~micro-SLPTX-Ssm6a, a unique 46-residue peptide from centipede~~ venom that ~~potently inhibits NaV1.7 with an IC50 of approximately 25 nM. micro-SLPTX-Ssm6a~~ has ~~more than 150-fold selectivity for NaV1.7 over all other human NaV subtypes, with~~ the ~~exception~~ of ~~NaV1.2, for which~~ the ~~selectivity is 32-fold~~. ~~micro~~-~~SLPTX~~-~~Ssm6a contains three disulfide bonds with~~ a unique ~~connectivity pattern,~~ and ~~it has no significant sequence homology with any previously characterized peptide or protein. micro-SLPTX-Ssm6a proved to be a more potent analgesic than morphine~~ in a ~~rodent model of chemical~~-~~induced pain~~, ~~and it was equipotent with morphine~~ in ~~rodent models of thermal~~ and ~~acid-induced pain~~. ~~This study establishes micro-SPTX-Ssm6a as~~ a ~~promising lead molecule~~ for the ~~development~~ of ~~novel analgesics targeting NaV1.7, which might be suitable for treating a wide range of human pain pathologies~~.	+	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.

-	~~Discovery~~ of a ~~selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models~~.,~~Yang S~~, ~~Xiao Y~~, ~~Kang~~ D, ~~Liu J~~, ~~Li Y~~, ~~Undheim EA~~, ~~Klint JK~~, ~~Rong M~~, ~~Lai R~~, King GF ~~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~~<ref>PMID:~~24082113~~</ref>	+	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<ref>PMID:26073605</ref>

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

OCA at 12:56, 24 June 2015

OCA — Wed, 24 Jun 2015 12:56:04 GMT

←Older revision		Revision as of 12:56, 24 June 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Solution structure of mu-SLPTX3-Ssm6a==
		+	<StructureSection load='2mun' size='340' side='right' caption='[[2mun]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2mun]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mun OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mun RCSB], [http://www.ebi.ac.uk/pdbsum/2mun PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Loss-of-function mutations in the human voltage-gated sodium channel NaV1.7 result in a congenital indifference to pain. Selective inhibitors of NaV1.7 are therefore likely to be powerful analgesics for treating a broad range of pain conditions. Herein we describe the identification of micro-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits NaV1.7 with an IC50 of approximately 25 nM. micro-SLPTX-Ssm6a has more than 150-fold selectivity for NaV1.7 over all other human NaV subtypes, with the exception of NaV1.2, for which the selectivity is 32-fold. micro-SLPTX-Ssm6a contains three disulfide bonds with a unique connectivity pattern, and it has no significant sequence homology with any previously characterized peptide or protein. micro-SLPTX-Ssm6a proved to be a more potent analgesic than morphine in a rodent model of chemical-induced pain, and it was equipotent with morphine in rodent models of thermal and acid-induced pain. This study establishes micro-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting NaV1.7, which might be suitable for treating a wide range of human pain pathologies.

-	~~The entry 2mun is ON HOLD until~~ Sep ~~13 2016~~	+	Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models.,Yang S, Xiao Y, Kang D, Liu J, Li Y, Undheim EA, Klint JK, Rong M, Lai R, King GF 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<ref>PMID:24082113</ref>

-	~~Authors: Undheim~~, E.A.~~B., King, G.F., Mobli, M~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Solution structure of mu-SLPTX3-Ssm6a~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: King, G F]]
	[[Category: Mobli, M]]		[[Category: Mobli, M]]
-	[[Category: Undheim, E.A.B]]	+	[[Category: Undheim, E A.B]]
-	[[Category: ~~King, G.F~~]]	+	[[Category: Crustacean hyperglycemic hormone]]
		+	[[Category: Ion channel inhibitor]]
		+	[[Category: Mu-slptx-ssm6a]]
		+	[[Category: Toxin]]

OCA at 12:26, 24 December 2014

OCA — Wed, 24 Dec 2014 12:26:31 GMT

←Older revision		Revision as of 12:26, 24 December 2014
Line 6:		Line 6:

	Description: Solution structure of mu-SLPTX3-Ssm6a		Description: Solution structure of mu-SLPTX3-Ssm6a
		+	[[Category: Unreleased Structures]]
		+	[[Category: Mobli, M]]
		+	[[Category: Undheim, E.A.B]]
		+	[[Category: King, G.F]]

OCA at 08:58, 20 October 2014

OCA — Mon, 20 Oct 2014 08:58:09 GMT

←Older revision		Revision as of 08:58, 20 October 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 2mun is ON HOLD	+	The entry 2mun is ON HOLD until Sep 13 2016

	Authors: Undheim, E.A.B., King, G.F., Mobli, M.		Authors: Undheim, E.A.B., King, G.F., Mobli, M.

	Description: Solution structure of mu-SLPTX3-Ssm6a		Description: Solution structure of mu-SLPTX3-Ssm6a

OCA: Protected "2mun" [edit=sysop:move=sysop]

OCA — Wed, 24 Sep 2014 07:29:32 GMT

Protected "2mun" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:29, 24 September 2014

OCA: New page: '''Unreleased structure''' The entry 2mun is ON HOLD Authors: Undheim, E.A.B., King, G.F., Mobli, M. Description: Solution structure of mu-SLPTX3-Ssm6a

OCA — Wed, 24 Sep 2014 07:29:31 GMT

New page: '''Unreleased structure''' The entry 2mun is ON HOLD Authors: Undheim, E.A.B., King, G.F., Mobli, M. Description: Solution structure of mu-SLPTX3-Ssm6a

New page

'''Unreleased structure'''

The entry 2mun is ON HOLD

Authors: Undheim, E.A.B., King, G.F., Mobli, M.

Description: Solution structure of mu-SLPTX3-Ssm6a