2nz9

From Proteopedia

(Difference between revisions)

Revision as of 06:36, 20 May 2020

Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2

Structural highlights

2nz9 is a 6 chain structure with sequence from Clostridium botulinum and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2nyy
Activity:	Bontoxilysin, with EC number 3.4.24.69
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BXA1_CLOBO] 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

Broadening antibody specificity without compromising affinity should facilitate detection and neutralization of toxin and viral subtypes. We used yeast display and a co-selection strategy to increase cross-reactivity of a single chain (sc) Fv antibody to botulinum neurotoxin type A (BoNT/A). Starting with a scFv that binds the BoNT/A1 subtype with high affinity (136 pM) and the BoNT/A2 subtype with low affinity (109 nM), we increased its affinity for BoNT/A2 1,250-fold, to 87 pM, while maintaining high-affinity binding to BoNT/A1 (115 pM). To find the molecular basis for improved cross-reactivity, we determined the X-ray co-crystal structures of wild-type and cross-reactive antibodies complexed to BoNT/A1 at resolutions up to 2.6 A, and measured the thermodynamic contribution of BoNT/A1 and A2 amino acids to wild-type and cross-reactive antibody binding. The results show how an antibody can be engineered to bind two different antigens despite structural differences in the antigen-antibody interface and may provide a general strategy for tuning antibody specificity and cross-reactivity.

Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin.,Garcia-Rodriguez C, Levy R, Arndt JW, Forsyth CM, Razai A, Lou J, Geren I, Stevens RC, Marks JD Nat Biotechnol. 2007 Jan;25(1):107-16. Epub 2006 Dec 17. PMID:17173035^[1]

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

References

↑ Garcia-Rodriguez C, Levy R, Arndt JW, Forsyth CM, Razai A, Lou J, Geren I, Stevens RC, Marks JD. Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Nat Biotechnol. 2007 Jan;25(1):107-16. Epub 2006 Dec 17. PMID:17173035 doi:10.1038/nbt1269

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/2nz9"

@@ Line 1: / Line 1: @@
 ==Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2==
-<StructureSection load='2nz9' size='340' side='right' caption='[[2nz9]], [[Resolution|resolution]] 3.79&Aring;' scene=''>
+<StructureSection load='2nz9' size='340' side='right'caption='[[2nz9]], [[Resolution|resolution]] 3.79&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2nz9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NZ9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2nz9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2NZ9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2nyy|2nyy]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nz9 OCA], [http://pdbe.org/2nz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nz9 RCSB], [http://www.ebi.ac.uk/pdbsum/2nz9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2nz9 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2nz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nz9 OCA], [http://pdbe.org/2nz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nz9 RCSB], [http://www.ebi.ac.uk/pdbsum/2nz9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2nz9 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 32: / Line 32: @@
 ==See Also==
-*[[Botulinum neurotoxin|Botulinum neurotoxin]]
+*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
 *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
@@ Line 41: / Line 41: @@
 [[Category: Clostridium botulinum]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Arndt, J W]]
 [[Category: Stevens, R C]]

2nz9

From Proteopedia

Revision as of 06:36, 20 May 2020

Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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