3aj6 | pdb_00003aj6
HA1 (HA33) mutant F179I of botulinum type C progenitor toxin complexed with N-acetylgalactosamine, bound at site II
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] Publication Abstract from PubMedA critical role in internalizing the Clostridium botulinum neurotoxin into gastrointestinal cells is played by nontoxic components complexed with the toxin. One of the components, a beta-trefoil lectin has been known as HA33 or HA1. The HA33 from C. botulinum type A (HA33/A) has been predicted to have a single sugar-binding site, while type C HA33 (HA33/C) has two sites. Here we constructed HA33/C mutants and evaluated the binding capacities of the individual sites through mucin-assay and isothermal titration calorimetry. The mutant W176A (site I knockout) had a K(d) value of 31.5mM for galactose (Gal) and 61.3mM for N-acetylgalactosamine (GalNAc), while the K(d) value for N-acetylneuraminic acid (Neu5Ac) was too high to be determined. In contrast, the double mutant N278A/Q279A (site II knockout) had a K(d) value of 11.8mM for Neu5Ac. We also determined the crystal structures of wild-type and the F179I mutant in complex with GalNAc at site II. The results suggest that site I of HA33/C is quite unique in that it mainly recognizes Neu5Ac, and site II seems less important for the lectin specificity. The architectures and the properties of the sugar-binding sites of HA33/C and HA33/A were shown to be drastically different. Molecular diversity of the two sugar-binding sites of the beta-trefoil lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin.,Nakamura T, Tonozuka T, Ito S, Takeda Y, Sato R, Matsuo I, Ito Y, Oguma K, Nishikawa A Arch Biochem Biophys. 2011 Aug 1;512(1):69-77. Epub 2011 May 26. PMID:21640703[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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