Structural basis of Lewis b antigen binding by the Helicobacter pylori adhesin BabA

• DOI: 10.1126/sciadv.1500315
• Publication Date: 2015-08-15T03:48:57Z
• Authors: Naim Hage; Tina Howard; Chris Phillips; Claire Brassington; Ross Overman; Judit Debreczeni; Paul Gellert; Snow Stolnik; G. Sebastiaan Win...; Franco H. Falcone
• Keywords: 0303 health sciences; 03 medical and health sciences; Helicobacter pylori; BabA; Bacterial adhesion; Adhesin; Research Articles; X-ray crystallography; 3. Good health

Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization the stomach, this Gram-negative bacterium adheres to Lewis(b) (Le(b)) antigens in mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, thus, molecular mechanism recognizing Le(b) remains unknown. We present crystal structure extracellular domain BabA, from H. strain J99, absence presence at 2.0- 2.1-Å resolutions, respectively. predominantly α-helical molecule with markedly kinked tertiary containing single, shallow binding site tip within β-strand motif. No conformational change occurs upon Le(b), which characterized by low affinity under acidic [K D (dissociation constant) ~227 μM] neutral (K ~252 μM) conditions. Binding mediated network hydrogen bonds between Fuc1, GlcNAc3, Fuc4, Gal5 residues total eight amino acids (C189, G191, N194, N206, D233, S234, S244, T246) through both carbonyl backbone side-chain interactions. The structural model was validated generation two variants N206A combined D233A/S244A substitutions, result reduction complete loss Knowledge basis recognition provides platform development therapeutics targeted inhibiting adherence mucosa.