3ah4
From Proteopedia
HA1 subcomponent of botulinum type C progenitor toxin complexed with galactose
Structural highlights
FunctionHA33C_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 PubMedClostridium 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. See AlsoReferences
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