|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Racemic structure of cyclic Vc1.1 (cVc1.1-1)== | | ==Racemic structure of cyclic Vc1.1 (cVc1.1-1)== |
| - | <StructureSection load='4ttl' size='340' side='right' caption='[[4ttl]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4ttl' size='340' side='right'caption='[[4ttl]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ttl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TTL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ttl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_victoriae Conus victoriae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TTL 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=4ttl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ttl OCA], [http://pdbe.org/4ttl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ttl RCSB], [http://www.ebi.ac.uk/pdbsum/4ttl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ttl ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7004Å</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=4ttl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ttl OCA], [https://pdbe.org/4ttl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ttl RCSB], [https://www.ebi.ac.uk/pdbsum/4ttl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ttl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CA1A_CONVC CA1A_CONVC]] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide (produced without hydroxyproline, nor 4-carboxyglutamate) is a neuronal nAChR antagonist that acts as a powerful analgesic. It blocks nAChRs composed of alpha-3 or -5/beta-2 (IC(50)=7.2 uM), alpha-3/beta-2 (IC(50)=7.3 uM), alpha-3/beta-4 (IC(50)=4.2 uM), alpha-3 or -5/beta-4 (IC(50)<30 uM), alpha-4/beta-2 (IC(50)<30 uM), alpha-4/beta-4 (IC(50)<30 uM) and alpha/beta/gamma/delta (IC(50)<30 uM) subunits.<ref>PMID:12779345</ref> <ref>PMID:15770155</ref> | + | [https://www.uniprot.org/uniprot/CA1A_CONVC CA1A_CONVC] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide (produced without hydroxyproline, nor 4-carboxyglutamate) is a neuronal nAChR antagonist that acts as a powerful analgesic. It blocks nAChRs composed of alpha-3 or -5/beta-2 (IC(50)=7.2 uM), alpha-3/beta-2 (IC(50)=7.3 uM), alpha-3/beta-4 (IC(50)=4.2 uM), alpha-3 or -5/beta-4 (IC(50)<30 uM), alpha-4/beta-2 (IC(50)<30 uM), alpha-4/beta-4 (IC(50)<30 uM) and alpha/beta/gamma/delta (IC(50)<30 uM) subunits.<ref>PMID:12779345</ref> <ref>PMID:15770155</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Craik, D J]] | + | [[Category: Conus victoriae]] |
| - | [[Category: King, G J]] | + | [[Category: Large Structures]] |
| - | [[Category: Wang, C K]] | + | [[Category: Craik DJ]] |
| - | [[Category: Cyclic peptide]] | + | [[Category: King GJ]] |
| - | [[Category: Disulfide bond]] | + | [[Category: Wang CK]] |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
CA1A_CONVC Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide (produced without hydroxyproline, nor 4-carboxyglutamate) is a neuronal nAChR antagonist that acts as a powerful analgesic. It blocks nAChRs composed of alpha-3 or -5/beta-2 (IC(50)=7.2 uM), alpha-3/beta-2 (IC(50)=7.3 uM), alpha-3/beta-4 (IC(50)=4.2 uM), alpha-3 or -5/beta-4 (IC(50)<30 uM), alpha-4/beta-2 (IC(50)<30 uM), alpha-4/beta-4 (IC(50)<30 uM) and alpha/beta/gamma/delta (IC(50)<30 uM) subunits.[1] [2]
Publication Abstract from PubMed
Cyclic disulfide-rich peptides have exceptional stability and are promising frameworks for drug design. We were interested in obtaining X-ray structures of these peptides to assist in drug design applications, but disulfide-rich peptides can be notoriously difficult to crystallize. To overcome this limitation, we chemically synthesized the L- and D-forms of three prototypic cyclic disulfide-rich peptides: SFTI-1 (14-mer with one disulfide bond), cVc1.1 (22-mer with two disulfide bonds), and kB1 (29-mer with three disulfide bonds) for racemic crystallization studies. Facile crystal formation occurred from a racemic mixture of each peptide, giving structures solved at resolutions from 1.25 A to 1.9 A. Additionally, we obtained the quasi-racemic structures of two mutants of kB1, [G6A]kB1, and [V25A]kB1, which were solved at a resolution of 1.25 A and 2.3 A, respectively. The racemic crystallography approach appears to have broad utility in the structural biology of cyclic peptides.
Racemic and Quasi-Racemic X-ray Structures of Cyclic Disulfide-Rich Peptide Drug Scaffolds.,Wang CK, King GJ, Northfield SE, Ojeda PG, Craik DJ Angew Chem Int Ed Engl. 2014 Aug 28. doi: 10.1002/anie.201406563. PMID:25168664[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sandall DW, Satkunanathan N, Keays DA, Polidano MA, Liping X, Pham V, Down JG, Khalil Z, Livett BG, Gayler KR. A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry. 2003 Jun 10;42(22):6904-11. PMID:12779345 doi:http://dx.doi.org/10.1021/bi034043e
- ↑ Lang PM, Burgstahler R, Haberberger RV, Sippel W, Grafe P. A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves. Neuroreport. 2005 Apr 4;16(5):479-83. PMID:15770155
- ↑ Wang CK, King GJ, Northfield SE, Ojeda PG, Craik DJ. Racemic and Quasi-Racemic X-ray Structures of Cyclic Disulfide-Rich Peptide Drug Scaffolds. Angew Chem Int Ed Engl. 2014 Aug 28. doi: 10.1002/anie.201406563. PMID:25168664 doi:http://dx.doi.org/10.1002/anie.201406563
|
