3ds9

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{{Seed}}
 
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[[Image:3ds9.png|left|200px]]
 
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==A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate==
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The line below this paragraph, containing "STRUCTURE_3ds9", creates the "Structure Box" on the page.
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<StructureSection load='3ds9' size='340' side='right'caption='[[3ds9]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3ds9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DS9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DS9 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.758&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=01W:(2S)-2-AMMONIO-4-[(2,4-DINITROPHENYL)AMINO]BUTANOATE'>01W</scene>, <scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3ds9| PDB=3ds9 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ds9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ds9 OCA], [https://pdbe.org/3ds9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ds9 RCSB], [https://www.ebi.ac.uk/pdbsum/3ds9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ds9 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BXA1_CLOBH BXA1_CLOBH] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ds/3ds9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ds9 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Botulinum neurotoxin serotype A is the most lethal of all known toxins. Here, we report the crystal structure, along with SAR data, of the zinc metalloprotease domain of BoNT/A bound to a potent peptidomimetic inhibitor (K(i)=41 nM) that resembles the local sequence of the SNAP-25 substrate. Surprisingly, the inhibitor adopts a helical conformation around the cleavage site, in contrast to the extended conformation of the native substrate. The backbone of the inhibitor's P1 residue displaces the putative catalytic water molecule and concomitantly interacts with the "proton shuttle" E224. This mechanism of inhibition is aided by residue contacts in the conserved S1' pocket of the substrate binding cleft and by the induction of new hydrophobic pockets, which are not present in the apo form, especially for the P2' residue of the inhibitor. Our inhibitor is specific for BoNT/A as it does not inhibit other BoNT serotypes or thermolysin.
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===A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate===
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A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate.,Zuniga JE, Schmidt JJ, Fenn T, Burnett JC, Arac D, Gussio R, Stafford RG, Badie SS, Bavari S, Brunger AT Structure. 2008 Oct 8;16(10):1588-97. PMID:18940613<ref>PMID:18940613</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3ds9" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18940613}}, adds the Publication Abstract to the page
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*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18940613 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18940613}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3DS9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DS9 OCA].
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==Reference==
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A Potent Peptidomimetic Inhibitor of Botulinum Neurotoxin Serotype A Has a Very Different Conformation than SNAP-25 Substrate., Zuniga JE, Schmidt JJ, Fenn T, Burnett JC, Arac D, Gussio R, Stafford RG, Badie SS, Bavari S, Brunger AT, Structure. 2008 Oct;16(10):1588-97. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18940613 18940613]
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[[Category: Bontoxilysin]]
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[[Category: Clostridium botulinum]]
[[Category: Clostridium botulinum]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Fenn, T.]]
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[[Category: Fenn T]]
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[[Category: Zuniga, J E.]]
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[[Category: Zuniga JE]]
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[[Category: Botulism]]
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[[Category: Hydrolase]]
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[[Category: Inhibition]]
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[[Category: Membrane]]
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[[Category: Metal-binding]]
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[[Category: Metalloprotease]]
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[[Category: Neuromuscular junction]]
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[[Category: Neurotoxin]]
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[[Category: Neurotransmission]]
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[[Category: Pharmaceutical]]
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[[Category: Protease]]
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[[Category: Secreted]]
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[[Category: Snare]]
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[[Category: Toxin]]
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[[Category: Transmembrane]]
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[[Category: Zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 29 09:43:25 2008''
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Current revision

A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate

PDB ID 3ds9

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