2h8i
From Proteopedia
(New page: 200px<br /><applet load="2h8i" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h8i, resolution 1.90Å" /> '''Crystal Structure of...) |
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| - | [[Image:2h8i.jpg|left|200px]]<br /><applet load="2h8i" size=" | + | [[Image:2h8i.jpg|left|200px]]<br /><applet load="2h8i" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2h8i, resolution 1.90Å" /> | caption="2h8i, resolution 1.90Å" /> | ||
'''Crystal Structure of the Bothropstoxin-I complexed with polyethylene glycol'''<br /> | '''Crystal Structure of the Bothropstoxin-I complexed with polyethylene glycol'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2H8I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu] with PEG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2H8I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu] with <scene name='pdbligand=PEG:'>PEG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H8I OCA]. |
==Reference== | ==Reference== | ||
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[[Category: myotoxicity]] | [[Category: myotoxicity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:48:47 2008'' |
Revision as of 12:48, 23 January 2008
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Crystal Structure of the Bothropstoxin-I complexed with polyethylene glycol
Overview
Lys49 phospholipase A2 homologues are highly myotoxic and cause extensive, tissue damage but do not display hydrolytic activity towards natural, phospholipids. The binding of heparin, heparin derivatives and polyanionic, compounds such as suramin result in partial inhibition (up to 60%) of the, myotoxic effects due to a change in the overall charge of the interfacial, surface. In vivo experiments demonstrate that polyethylene glycol inhibits, more than 90% of the myotoxic effects without exhibiting secondary toxic, effects. The crystal structure of bothropstoxin-I complexed with, polyethylene glycol reveals that this inhibition is due to steric, hindrance of the access to the PLA2-active site-like region. These two, inhibitory pathways indicate the roles of the overall surface charge and, free accessibility to the PLA2-active site-like region in the functioning, of Lys49 phospholipases A2 homologues. Molecular dynamics simulations, small angle X-ray scattering and structural analysis indicate that the, oligomeric states both in solution and in the crystalline states of Lys49, phospholipases A2 are principally mediated by hydrophobic contacts formed, between the interfacial surfaces. These results provide the framework for, the potential application of both clinically approved drugs for the, treatment of Viperidae snakebites.
About this Structure
2H8I is a Single protein structure of sequence from Bothrops jararacussu with as ligand. Full crystallographic information is available from OCA.
Reference
Interfacial surface charge and free accessibility to the PLA2-active site-like region are essential requirements for the activity of Lys49 PLA2 homologues., Murakami MT, Vicoti MM, Abrego JR, Lourenzoni MR, Cintra AC, Arruda EZ, Tomaz MA, Melo PA, Arni RK, Toxicon. 2007 Mar 1;49(3):378-87. Epub 2006 Nov 3. PMID:17157889
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