3AH1

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

Replaces:  2EHI

Summary for 3AH1

• Entry DOI: 10.2210/pdb3ah1/pdb
• Related: 1QXM 3AH2 3AH4
• Descriptor: Main hemagglutinin component, N-acetyl-beta-neuraminic acid (3 entities in total)
• Functional Keywords: toxin, beta trefoil, hemagglutinin
• Biological source: Clostridium botulinum
• Total number of polymer chains: 2
• Total formula weight: 69085.52

Authors

Nakamura, T.,Tonozuka, T.,Ide, A.,Yuzawa, T.,Oguma, K.,Nishikawa, A. (deposition date: 2010-04-13, release date: 2010-04-28, Last modification date: 2023-11-01)

Primary citation

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., 376:854-867, 2008

PubMed Abstract: 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.

PubMed: 18178224
DOI: 10.1016/j.jmb.2007.12.031

Experimental method

X-RAY DIFFRACTION (2.2 Å)