3ah1

From Proteopedia

(Difference between revisions)

Current revision

HA1 subcomponent of botulinum type C progenitor toxin complexed with N-acetylneuramic acid

Structural highlights

3ah1 is a 2 chain structure with sequence from Clostridium botulinum. This structure supersedes the now removed PDB entry 2ehi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HA33C_CBCP Agglutinates human erythrocytes (PubMed:2205574). The hemagglutinin (HA) component of the progenitor toxin protects the structural integrity of botulinum neurotoxin; may increase internalization of the neurotoxin into the bloodstream of the host (PubMed:9421908). The hemagglutinin (HA) component is involved in binding to the upper small intestine through interactions with glycolipids and glycoproteins containing sialic acid moieties (Probable). Binds galactose or oligosaccharides with galactose at their non-reducing end (PubMed:14663070). Binds eukaryotic host mucins; binding is inhibited by N-acetyl-beta-neuraminic acid, N-acetyl-D-galactosamine, galactose, and methyl N-acetyl-beta-neuraminic acid (PubMed:18178224). Binds N-acetyl-beta-neuraminic acid, N-acetyl-D-galactosamine and galactose (but not glucose) via 2 sites (PubMed:18178224, PubMed:21640703).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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

Clostridium botulinum type C 16S progenitor toxin contains a hemagglutinin (HA) subcomponent, designated HA1, which appears to play an important role in the effective internalization of the toxin in gastrointestinal epithelial cells and in creating a broad specificity for the oligosaccharide structure that corresponds to various targets. In this study, using the recombinant protein fused to glutathione S-transferase, we investigated the binding specificity of the HA1 subcomponent to sugars and estimated the binding sites of HA1 based on X-ray crystallography and soaking experiments using various sugars. N-Acetylneuraminic acid, N-acetylgalactosamine, and galactose effectively inhibited the binding that occurs between glutathione S-transferase-HA1 and mucins, whereas N-acetylglucosamine and glucose did not inhibit it. The crystal structures of HA1 complex with N-acetylneuraminic acid, N-acetylgalactosamine, and galactose were also determined. There are two sugar-binding sites, sites I and II. Site I corresponds to the electron densities noted for all sugars and is located at the C-terminal beta-trefoil domain, while site II corresponds to the electron densities noted only for galactose. An aromatic amino acid residue, Trp176, at site I has a stacking interaction with the hexose ring of the sugars. On the other hand, there is no aromatic residue at site II; thus, the interaction with galactose seems to be poor. The double mutant W176A at site I and D271F at site II has no avidity for N-acetylneuraminic acid but has avidity for galactose. In this report, the binding specificity of botulinum C16S toxin HA1 to various sugars is demonstrated based on its structural features.

Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.,Nakamura T, Tonozuka T, Ide A, Yuzawa T, Oguma K, Nishikawa A J Mol Biol. 2008 Feb 22;376(3):854-67. Epub 2007 Dec 23. PMID:18178224^[7]

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

References

↑ Inoue K, Sobhany M, Transue TR, Oguma K, Pedersen LC, Negishi M. Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum. Microbiology. 2003 Dec;149(Pt 12):3361-70. PMID:14663070
↑ Nakamura T, Tonozuka T, Ide A, Yuzawa T, Oguma K, Nishikawa A. Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin. J Mol Biol. 2008 Feb 22;376(3):854-67. Epub 2007 Dec 23. PMID:18178224 doi:10.1016/j.jmb.2007.12.031
↑ Nakamura T, Tonozuka T, Ito S, Takeda Y, Sato R, Matsuo I, Ito Y, Oguma K, Nishikawa A. Molecular diversity of the two sugar-binding sites of the beta-trefoil lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin. Arch Biochem Biophys. 2011 Aug 1;512(1):69-77. Epub 2011 May 26. PMID:21640703 doi:10.1016/j.abb.2011.05.012
↑ Tsuzuki K, Kimura K, Fujii N, Yokosawa N, Indoh T, Murakami T, Oguma K. Cloning and complete nucleotide sequence of the gene for the main component of hemagglutinin produced by Clostridium botulinum type C. Infect Immun. 1990 Oct;58(10):3173-7. PMID:2205574 doi:10.1128/iai.58.10.3173-3177.1990
↑ Fujinaga Y, Inoue K, Watanabe S, Yokota K, Hirai Y, Nagamachi E, Oguma K. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin. Microbiology (Reading). 1997 Dec;143 ( Pt 12):3841-3847. doi:, 10.1099/00221287-143-12-3841. PMID:9421908 doi:http://dx.doi.org/10.1099/00221287-143-12-3841
↑ Fujinaga Y, Inoue K, Watanabe S, Yokota K, Hirai Y, Nagamachi E, Oguma K. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin. Microbiology (Reading). 1997 Dec;143 ( Pt 12):3841-3847. doi:, 10.1099/00221287-143-12-3841. PMID:9421908 doi:http://dx.doi.org/10.1099/00221287-143-12-3841
↑ Nakamura T, Tonozuka T, Ide A, Yuzawa T, Oguma K, Nishikawa A. Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin. J Mol Biol. 2008 Feb 22;376(3):854-67. Epub 2007 Dec 23. PMID:18178224 doi:10.1016/j.jmb.2007.12.031

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/3ah1"

@@ Line 3: / Line 3: @@
 <StructureSection load='3ah1' size='340' side='right'caption='[[3ah1]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3ah1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ehi 2ehi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AH1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3AH1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3ah1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ehi 2ehi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AH1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AH1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qxm|1qxm]], [[3ah2|3ah2]], [[3ah4|3ah4]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></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=3ah1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ah1 OCA], [http://pdbe.org/3ah1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ah1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ah1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ah1 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ah1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ah1 OCA], [https://pdbe.org/3ah1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ah1 RCSB], [https://www.ebi.ac.uk/pdbsum/3ah1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ah1 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/HA33_CLOBO HA33_CLOBO]] Protects the structural integrity of the neurotoxin; may increase internalization of the neurotoxin into the bloodstream of the host. Involved in binding to the small intestine through interactions with glycolipids and glycoproteins containing sialic acid moieties.
+[https://www.uniprot.org/uniprot/HA33C_CBCP HA33C_CBCP] Agglutinates human erythrocytes (PubMed:2205574). The hemagglutinin (HA) component of the progenitor toxin protects the structural integrity of botulinum neurotoxin; may increase internalization of the neurotoxin into the bloodstream of the host (PubMed:9421908). The hemagglutinin (HA) component is involved in binding to the upper small intestine through interactions with glycolipids and glycoproteins containing sialic acid moieties (Probable). Binds galactose or oligosaccharides with galactose at their non-reducing end (PubMed:14663070). Binds eukaryotic host mucins; binding is inhibited by N-acetyl-beta-neuraminic acid, N-acetyl-D-galactosamine, galactose, and methyl N-acetyl-beta-neuraminic acid (PubMed:18178224). Binds N-acetyl-beta-neuraminic acid, N-acetyl-D-galactosamine and galactose (but not glucose) via 2 sites (PubMed:18178224, PubMed:21640703).<ref>PMID:14663070</ref> <ref>PMID:18178224</ref> <ref>PMID:21640703</ref> <ref>PMID:2205574</ref> <ref>PMID:9421908</ref> <ref>PMID:9421908</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Bacillus botulinus van ermengem 1896]]
+[[Category: Clostridium botulinum]]
 [[Category: Large Structures]]
-[[Category: Ide, A]]
+[[Category: Ide A]]
-[[Category: Nakamura, T]]
+[[Category: Nakamura T]]
-[[Category: Nishikawa, A]]
+[[Category: Nishikawa A]]
-[[Category: Oguma, K]]
+[[Category: Oguma K]]
-[[Category: Tonozuka, T]]
+[[Category: Tonozuka T]]
-[[Category: Yuzawa, T]]
+[[Category: Yuzawa T]]
-[[Category: Beta trefoil]]
-[[Category: Hemagglutinin]]
-[[Category: Toxin]]

3ah1

From Proteopedia

Current revision

HA1 subcomponent of botulinum type C progenitor toxin complexed with N-acetylneuramic acid

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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