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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[3plc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Ophiophagus_hannah Ophiophagus hannah]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PLC FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3plc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Ophiophagus_hannah Ophiophagus hannah]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PLC 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=3plc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3plc OCA], [https://pdbe.org/3plc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3plc RCSB], [https://www.ebi.ac.uk/pdbsum/3plc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3plc 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]] 2.41Å</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=3plc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3plc OCA], [https://pdbe.org/3plc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3plc RCSB], [https://www.ebi.ac.uk/pdbsum/3plc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3plc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/3FBC7_OPHHA 3FBC7_OPHHA]] Acts as a beta-blocker by binding to beta-1 and beta-2 adrenergic receptors (ADRB1 and ADRB2). It dose-dependently decreases the heart rate (bradycardia), whereas conventional cardiotoxins increases it. At 100 mg/kg, intraperitoneal injection into mice provokes labored breathing, impaired locomotion, lack of response to external stimuli, and death (after 30 min).<ref>PMID:17616557</ref>
| + | [https://www.uniprot.org/uniprot/3SDC7_OPHHA 3SDC7_OPHHA] Acts as a beta-blocker by binding to beta-1 and beta-2 adrenergic receptors (ADRB1 and ADRB2). It dose-dependently decreases the heart rate (bradycardia), whereas conventional cardiotoxins increases it. At 100 mg/kg, intraperitoneal injection into mice provokes labored breathing, impaired locomotion, lack of response to external stimuli, and death (after 30 min).<ref>PMID:17616557</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Ophiophagus hannah]] | | [[Category: Ophiophagus hannah]] |
| - | [[Category: Kini, R M]] | + | [[Category: Kini RM]] |
| - | [[Category: Qingxiang, S]] | + | [[Category: Qingxiang S]] |
| - | [[Category: Roy, A]] | + | [[Category: Roy A]] |
| - | [[Category: Sivaraman, J]] | + | [[Category: Sivaraman J]] |
| - | [[Category: Beta-cardiotoxin]]
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| - | [[Category: Beta-sheet]]
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| - | [[Category: Novel cardiotoxin]]
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| - | [[Category: Toxin]]
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| Structural highlights
Function
3SDC7_OPHHA Acts as a beta-blocker by binding to beta-1 and beta-2 adrenergic receptors (ADRB1 and ADRB2). It dose-dependently decreases the heart rate (bradycardia), whereas conventional cardiotoxins increases it. At 100 mg/kg, intraperitoneal injection into mice provokes labored breathing, impaired locomotion, lack of response to external stimuli, and death (after 30 min).[1]
Publication Abstract from PubMed
beta-Cardiotoxin is a novel member of the snake venom three-finger toxin (3FTX) family. This is the first exogenous protein to antagonize beta-adrenergic receptors and thereby causing reduction in heart rates (bradycardia) when administered into animals, unlike the conventional cardiotoxins as reported earlier. 3FTXs are stable all beta-sheet peptides with 60-80 amino acid residues. Here, we describe the three-dimensional crystal structure of beta-cardiotoxin together with the identification of a molten globule intermediate in the unfolding pathway of this protein. In spite of the overall structural similarity of this protein with conventional cardiotoxins, there are notable differences observed at the loop region and in the charge distribution on the surface, which are known to be critical for cytolytic activity of cardiotoxins. The molten globule intermediate state present in the thermal unfolding pathway of beta-cardiotoxin was however not observed during the chemical denaturation of the protein. Interestingly, circular dichroism (CD) and NMR studies revealed the presence of alpha-helical secondary structure in the molten globule intermediate. These results point to substantial conformational plasticity of beta-cardiotoxin, which might aid the protein in responding to the sometimes conflicting demands of structure, stability, and function during its biological lifetime.
Identification of a alpha-helical molten globule intermediate and structural characterization of beta-cardiotoxin, an all beta-sheet protein isolated from the venom of Ophiophagus hannah (king cobra).,Roy A, Qingxiang S, Alex C, Rajagopalan N, Jobichen C, Sivaraman J, Kini RM Protein Sci. 2019 May;28(5):952-963. doi: 10.1002/pro.3605. Epub 2019 Apr 4. PMID:30891862[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rajagopalan N, Pung YF, Zhu YZ, Wong PT, Kumar PP, Kini RM. Beta-cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity. FASEB J. 2007 Nov;21(13):3685-95. Epub 2007 Jul 6. PMID:17616557 doi:http://dx.doi.org/fj.07-8658com
- ↑ Roy A, Qingxiang S, Alex C, Rajagopalan N, Jobichen C, Sivaraman J, Kini RM. Identification of a alpha-helical molten globule intermediate and structural characterization of beta-cardiotoxin, an all beta-sheet protein isolated from the venom of Ophiophagus hannah (king cobra). Protein Sci. 2019 May;28(5):952-963. doi: 10.1002/pro.3605. Epub 2019 Apr 4. PMID:30891862 doi:http://dx.doi.org/10.1002/pro.3605
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