1bun
From Proteopedia
(New page: 200px<br /><applet load="1bun" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bun, resolution 2.45Å" /> '''STRUCTURE OF BETA2-B...) |
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| - | [[Image:1bun.gif|left|200px]]<br /><applet load="1bun" size=" | + | [[Image:1bun.gif|left|200px]]<br /><applet load="1bun" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1bun, resolution 2.45Å" /> | caption="1bun, resolution 2.45Å" /> | ||
'''STRUCTURE OF BETA2-BUNGAROTOXIN: POTASSIUM CHANNEL BINDING BY KUNITZ MODULES AND TARGETED PHOSPHOLIPASE ACTION'''<br /> | '''STRUCTURE OF BETA2-BUNGAROTOXIN: POTASSIUM CHANNEL BINDING BY KUNITZ MODULES AND TARGETED PHOSPHOLIPASE ACTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: beta-bungarotoxin is a heterodimeric neurotoxin consisting of | + | BACKGROUND: beta-bungarotoxin is a heterodimeric neurotoxin consisting of a phospholipase subunit linked by a disulfide bond to a K+ channel binding subunit which is a member of the Kunitz protease inhibitor superfamily. Toxicity, characterized by blockage of neural transmission, is achieved by the lipolytic action of the phospholipase targeted to the presynaptic membrane by the Kunitz module. RESULTS: The crystal structure at 2.45 A resolution suggests that the ion channel binding region of the Kunitz subunit is at the opposite end of the module from the loop typically involved in protease binding. Analysis of the phospholipase subunit reveals a partially occluded substrate-binding surface and reduced hydrophobicity. CONCLUSIONS: Molecular recognition by this Kunitz module appears to diverge considerably from more conventional superfamily members. The ion channel binding region identified here may mimic the regulatory interaction of endogenous neuropeptides. Adaptations of the phospholipase subunit make it uniquely suited to targeting and explain the remarkable ability of the toxin to avoid binding to non-target membranes. Insight into the mechanism of beta-bungarotoxin gained here may lead to the development of therapeutic strategies against not only pathological cells, but also enveloped viruses. |
==About this Structure== | ==About this Structure== | ||
| - | 1BUN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] with NA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http:// | + | 1BUN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] with <scene name='pdbligand=NA:'>NA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BUN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Hendrickson, W | + | [[Category: Hendrickson, W A.]] |
| - | [[Category: Kwong, P | + | [[Category: Kwong, P D.]] |
| - | [[Category: Mcdonald, N | + | [[Category: Mcdonald, N Q.]] |
| - | [[Category: Sigler, P | + | [[Category: Sigler, P B.]] |
[[Category: NA]] | [[Category: NA]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: presynaptic neurotoxin]] | [[Category: presynaptic neurotoxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:59:17 2008'' |
Revision as of 09:59, 21 February 2008
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STRUCTURE OF BETA2-BUNGAROTOXIN: POTASSIUM CHANNEL BINDING BY KUNITZ MODULES AND TARGETED PHOSPHOLIPASE ACTION
Overview
BACKGROUND: beta-bungarotoxin is a heterodimeric neurotoxin consisting of a phospholipase subunit linked by a disulfide bond to a K+ channel binding subunit which is a member of the Kunitz protease inhibitor superfamily. Toxicity, characterized by blockage of neural transmission, is achieved by the lipolytic action of the phospholipase targeted to the presynaptic membrane by the Kunitz module. RESULTS: The crystal structure at 2.45 A resolution suggests that the ion channel binding region of the Kunitz subunit is at the opposite end of the module from the loop typically involved in protease binding. Analysis of the phospholipase subunit reveals a partially occluded substrate-binding surface and reduced hydrophobicity. CONCLUSIONS: Molecular recognition by this Kunitz module appears to diverge considerably from more conventional superfamily members. The ion channel binding region identified here may mimic the regulatory interaction of endogenous neuropeptides. Adaptations of the phospholipase subunit make it uniquely suited to targeting and explain the remarkable ability of the toxin to avoid binding to non-target membranes. Insight into the mechanism of beta-bungarotoxin gained here may lead to the development of therapeutic strategies against not only pathological cells, but also enveloped viruses.
About this Structure
1BUN is a Protein complex structure of sequences from Bungarus multicinctus with as ligand. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
Structure of beta 2-bungarotoxin: potassium channel binding by Kunitz modules and targeted phospholipase action., Kwong PD, McDonald NQ, Sigler PB, Hendrickson WA, Structure. 1995 Oct 15;3(10):1109-19. PMID:8590005
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