2w2d

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of a Catalytically Active, Non-toxic Endopeptidase Derivative of Clostridium botulinum Toxin A

Structural highlights

2w2d is a 4 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.59Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Botulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.

Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A.,Masuyer G, Thiyagarajan N, James PL, Marks PM, Chaddock JA, Acharya KR Biochem Biophys Res Commun. 2009 Mar 27;381(1):50-3. Epub 2009 Feb 8. PMID:19351593^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Masuyer G, Thiyagarajan N, James PL, Marks PM, Chaddock JA, Acharya KR. Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A. Biochem Biophys Res Commun. 2009 Mar 27;381(1):50-3. Epub 2009 Feb 8. PMID:19351593 doi:10.1016/j.bbrc.2009.02.003

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2w2d"

@@ Line 1: / Line 1: @@
-[[Image:2w2d.png|left|200px]]
-<!--
+==Crystal Structure of a Catalytically Active, Non-toxic Endopeptidase Derivative of Clostridium botulinum Toxin A==
-The line below this paragraph, containing "STRUCTURE_2w2d", creates the "Structure Box" on the page.
+<StructureSection load='2w2d' size='340' side='right'caption='[[2w2d]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2w2d]] is a 4 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=2W2D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W2D FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.59&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_2w2d|  PDB=2w2d  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2w2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w2d OCA], [https://pdbe.org/2w2d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w2d RCSB], [https://www.ebi.ac.uk/pdbsum/2w2d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w2d ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w2/2w2d_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2w2d ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Botulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.
-===Crystal Structure of a Catalytically Active, Non-toxic Endopeptidase Derivative of Clostridium botulinum Toxin A===
+Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A.,Masuyer G, Thiyagarajan N, James PL, Marks PM, Chaddock JA, Acharya KR Biochem Biophys Res Commun. 2009 Mar 27;381(1):50-3. Epub 2009 Feb 8. PMID:19351593<ref>PMID:19351593</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2w2d" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19351593}}, adds the Publication Abstract to the page
+*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19351593 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19351593}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[2w2d]] is a 4 chain structure with sequence 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=2W2D OCA].
-==Reference==
-<ref group="xtra">PMID:019351593</ref><references group="xtra"/>
-[[Category: Bontoxilysin]]
 [[Category: Clostridium botulinum]]
-[[Category: Acharya, K R.]]
+[[Category: Large Structures]]
-[[Category: Chaddock, J A.]]
+[[Category: Acharya KR]]
-[[Category: James, P L.]]
+[[Category: Chaddock JA]]
-[[Category: Marks, P M.H.]]
+[[Category: James PL]]
-[[Category: Masuyer, G.]]
+[[Category: Marks PMH]]
-[[Category: Thiyagarajan, N.]]
+[[Category: Masuyer G]]
-[[Category: Bont]]
+[[Category: Thiyagarajan N]]
-[[Category: Hydrolase]]
-[[Category: Membrane]]
-[[Category: Membrane domain]]
-[[Category: Metal-binding]]
-[[Category: Metalloprotease]]
-[[Category: Mixed alpha and beta]]
-[[Category: Neurotoxin]]
-[[Category: Protease]]
-[[Category: Protein engineering]]
-[[Category: Secreted]]
-[[Category: Transmembrane]]
-[[Category: Zinc protease]]

2w2d

From Proteopedia

Current revision

Crystal Structure of a Catalytically Active, Non-toxic Endopeptidase Derivative of Clostridium botulinum Toxin A

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox