title: Modeling and biochemical analysis of the activity of antibiofilm agent Dispersin B.
abstract: Bacteria in a biofilm are enmeshed in a self-synthesized extracellular polysaccharide matrix (PGA), which is a linear polymer of beta(1,6)-linked N-acetylglucosamine (GlcNAc) residues. Dispersin B (DspB), a soluble glycoside hydrolase produced by the periodontal pathogen Actinobacillus actinomycetemcomitans degrades PGA. The enzyme DspB is an alpha/beta TIM-barrel protein and belongs to family 20 glycosyl hydrolases members. The enzyme activity of DspB with regard to its substrate specificity towards beta(1,6)-linked GlcNAc polymers and its endo/exo character was investigated through ligand docking and the hydrolysis of synthetic oligosaccharides. Ligand docking analysis suggested that beta(1,6)-linked GlcNAc oligosaccharide bound to the active site better that beta(1,4)-linked GlcNAc oligosaccharide. Our combined results indicate that DspB is an exo-acting enzyme that hydrolyzes beta(1,6)-linked N-acetylglucosamine oligomers.
authors.affiliation: Academic Systems and Technologies, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Kerrigan
authors.forename: C
authors.initials: C
authors.lastname: Ragunath
authors.forename: Lili
authors.initials: L
authors.lastname: Kandra
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Gyémánt
authors.forename: A
authors.initials: A
authors.lastname: Lipták
authors.forename: L
authors.initials: L
authors.lastname: Jánossy
authors.forename: J B
authors.initials: JB
authors.lastname: Kaplan
authors.forename: N
authors.initials: N
authors.lastname: Ramasubbu
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000201:enzymology / Q000235:genetics; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002240:Carbohydrate Sequence; D020134:Catalytic Domain; D004926:Escherichia coli / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006868:Hydrolysis; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; D006026:Glycoside Hydrolases; C501330:dispersin B, Actinobacillus actinomycetemcomitans