1g9c
From Proteopedia
(New page: 200px<br /><applet load="1g9c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g9c, resolution 2.35Å" /> '''CRYSTAL STRUCTURE OF...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1g9c.jpg|left|200px]]<br /><applet load="1g9c" size=" | + | [[Image:1g9c.jpg|left|200px]]<br /><applet load="1g9c" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1g9c, resolution 2.35Å" /> | caption="1g9c, resolution 2.35Å" /> | ||
'''CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 4)'''<br /> | '''CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 4)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Clostridium botulinum neurotoxins are zinc endopeptidase proteins | + | Clostridium botulinum neurotoxins are zinc endopeptidase proteins responsible for cleaving specific peptide bonds of proteins of neuroexocytosis apparatus. The ability of drugs to interfere with toxin's catalytic activity is being evaluated with zinc chelators and metalloprotease inhibitors. It is important to develop effective pharmacological treatment for the intact holotoxin before the catalytic domain separates and enters the cytosol. We present here evidence for a novel mechanism of an inhibitor binding to the holotoxin and for the chelation of zinc from our structural studies on Clostridium botulinum neurotoxin type B in complex with a potential metalloprotease inhibitor, bis(5-amidino-2-benzimidazolyl)methane, and provide snapshots of the reaction as it progresses. The binding and inhibition mechanism of this inhibitor to the neurotoxin seems to be unique for intact botulinum neurotoxins. The environment of the active site rearranges in the presence of the inhibitor, and the zinc ion is gradually removed from the active site and transported to a different site in the protein, probably causing loss of catalytic activity. |
==About this Structure== | ==About this Structure== | ||
| - | 1G9C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] with ZN and BAB as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] Full crystallographic information is available from [http:// | + | 1G9C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=BAB:'>BAB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G9C OCA]. |
==Reference== | ==Reference== | ||
| Line 23: | Line 23: | ||
[[Category: neurotoxin]] | [[Category: neurotoxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:47:36 2008'' |
Revision as of 10:47, 21 February 2008
|
CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 4)
Overview
Clostridium botulinum neurotoxins are zinc endopeptidase proteins responsible for cleaving specific peptide bonds of proteins of neuroexocytosis apparatus. The ability of drugs to interfere with toxin's catalytic activity is being evaluated with zinc chelators and metalloprotease inhibitors. It is important to develop effective pharmacological treatment for the intact holotoxin before the catalytic domain separates and enters the cytosol. We present here evidence for a novel mechanism of an inhibitor binding to the holotoxin and for the chelation of zinc from our structural studies on Clostridium botulinum neurotoxin type B in complex with a potential metalloprotease inhibitor, bis(5-amidino-2-benzimidazolyl)methane, and provide snapshots of the reaction as it progresses. The binding and inhibition mechanism of this inhibitor to the neurotoxin seems to be unique for intact botulinum neurotoxins. The environment of the active site rearranges in the presence of the inhibitor, and the zinc ion is gradually removed from the active site and transported to a different site in the protein, probably causing loss of catalytic activity.
About this Structure
1G9C is a Single protein structure of sequence from Clostridium botulinum with and as ligands. Active as Bontoxilysin, with EC number 3.4.24.69 Full crystallographic information is available from OCA.
Reference
A novel mechanism for Clostridium botulinum neurotoxin inhibition., Eswaramoorthy S, Kumaran D, Swaminathan S, Biochemistry. 2002 Aug 6;41(31):9795-802. PMID:12146945
Page seeded by OCA on Thu Feb 21 12:47:36 2008
