|
|
| (2 intermediate revisions not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='1ug4' size='340' side='right'caption='[[1ug4]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='1ug4' size='340' side='right'caption='[[1ug4]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ug4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UG4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ug4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UG4 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=1ug4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ug4 OCA], [http://pdbe.org/1ug4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ug4 RCSB], [http://www.ebi.ac.uk/pdbsum/1ug4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ug4 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]] 1.6Å</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=1ug4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ug4 OCA], [https://pdbe.org/1ug4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ug4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ug4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ug4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/3SAN_NAJAT 3SAN_NAJAT]] Basic protein that bind to cell membrane and depolarizes cardiomyocytes. This cytotoxin also shows lytic activities, on many other cells including red blood cells. Interaction with sulfatides in the cell membrane induces pore formation and cell internalization and is responsible for cytotoxicity in cardiomyocytes. It targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. Inhibits protein kinases C (By similarity). It binds to the integrin alpha-V/beta-3 with a moderate affinity (PubMed:16407244).<ref>PMID:16407244</ref> | + | [https://www.uniprot.org/uniprot/3SAN_NAJAT 3SAN_NAJAT] Basic protein that bind to cell membrane and depolarizes cardiomyocytes. This cytotoxin also shows lytic activities, on many other cells including red blood cells. Interaction with sulfatides in the cell membrane induces pore formation and cell internalization and is responsible for cytotoxicity in cardiomyocytes. It targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. Inhibits protein kinases C (By similarity). It binds to the integrin alpha-V/beta-3 with a moderate affinity (PubMed:16407244).<ref>PMID:16407244</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 13: |
Line 14: |
| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ug/1ug4_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ug/1ug4_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| Line 36: |
Line 37: |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Naja atra]] | | [[Category: Naja atra]] |
| - | [[Category: Chen, C J]] | + | [[Category: Chen C-J]] |
| - | [[Category: Chung, F Y]] | + | [[Category: Chung F-Y]] |
| - | [[Category: Wu, W G]] | + | [[Category: Wu W-G]] |
| - | [[Category: Cardiotoxin]]
| + | |
| - | [[Category: Cobra]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Venom]]
| + | |
| Structural highlights
Function
3SAN_NAJAT Basic protein that bind to cell membrane and depolarizes cardiomyocytes. This cytotoxin also shows lytic activities, on many other cells including red blood cells. Interaction with sulfatides in the cell membrane induces pore formation and cell internalization and is responsible for cytotoxicity in cardiomyocytes. It targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. Inhibits protein kinases C (By similarity). It binds to the integrin alpha-V/beta-3 with a moderate affinity (PubMed:16407244).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Natural homologues of cobra cardiotoxins (CTXs) were classified into two structural subclasses of group I and II based on the amino acid sequence and circular dichroism analysis, but the exact differences in their three-dimensional structures and biological significance remain elusive. We show by circular dichroism, NMR spectroscopic, and X-ray crystallographic analyses of a newly purified group I CTX A6 from eastern Taiwan cobra (Naja atra) venoms that its loop I conformation adopts a type VIa turn with a cis peptide bond located between two proline residues of PPxY. A similar "banana-twisted" conformation can be observed in other group I CTXs and also in cyclolinopeptide A and its analogues. By binding to the membrane environment, group I CTX undergoes a conformational change to adopt a more extended hydrophobic domain with beta-sheet twisting closer to the one adopted by group II CTX. This result resolves a discrepancy in the CTX structural difference reported previously between solution as well as crystal state and shows that, in addition to the hydrophobicity, the exact loop I conformation also plays an important role in CTX-membrane interaction. Potential protein targets of group I CTXs after cell internalization are also discussed on the basis of the determined loop I conformation.
Structural difference between group I and group II cobra cardiotoxins: X-ray, NMR, and CD analysis of the effect of cis-proline conformation on three-fingered toxins.,Chen TS, Chung FY, Tjong SC, Goh KS, Huang WN, Chien KY, Wu PL, Lin HC, Chen CJ, Wu WG Biochemistry. 2005 May 24;44(20):7414-26. PMID:15895985[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu PL, Lee SC, Chuang CC, Mori S, Akakura N, Wu WG, Takada Y. Non-cytotoxic cobra cardiotoxin A5 binds to alpha(v)beta3 integrin and inhibits bone resorption. Identification of cardiotoxins as non-RGD integrin-binding proteins of the Ly-6 family. J Biol Chem. 2006 Mar 24;281(12):7937-45. Epub 2006 Jan 10. PMID:16407244 doi:http://dx.doi.org/M513035200
- ↑ Chen TS, Chung FY, Tjong SC, Goh KS, Huang WN, Chien KY, Wu PL, Lin HC, Chen CJ, Wu WG. Structural difference between group I and group II cobra cardiotoxins: X-ray, NMR, and CD analysis of the effect of cis-proline conformation on three-fingered toxins. Biochemistry. 2005 May 24;44(20):7414-26. PMID:15895985 doi:10.1021/bi050172e
|
