4ZH7: Structural Basis Of Lewisb Antigen Binding By The Helicobacter Pylori Adhesin Baba

Citation:
Abstract
Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewisb (Leb) antigens in the gastric mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, and thus, its molecular mechanism for recognizing Leb antigens remains unknown. We present the crystal structure of the extracellular domain of BabA, from H. pylori strain J99, in the absence and presence of Leb at 2.0- and 2.1-A resolutions, respectively. BabA is a predominantly alpha-helical molecule with a markedly kinked tertiary structure containing a single, shallow Leb binding site at its tip within a beta-strand motif. No conformational change occurs in BabA upon binding of Leb, which is characterized by low affinity under acidic [K D (dissociation constant) of ~227 muM] and neutral (K D of ~252 muM) conditions. Binding is mediated by a network of hydrogen bonds between Leb Fuc1, GlcNAc3, Fuc4, and Gal5 residues and a total of eight BabA amino acids (C189, G191, N194, N206, D233, S234, S244, and T246) through both carbonyl backbone and side-chain interactions. The structural model was validated through the generation of two BabA variants containing N206A and combined D233A/S244A substitutions, which result in a reduction and complete loss of binding affinity to Leb, respectively. Knowledge of the molecular basis of Leb recognition by BabA provides a platform for the development of therapeutics targeted at inhibiting H. pylori adherence to the gastric mucosa.
PDB ID: 4ZH7Download
MMDB ID: 131926
PDB Deposition Date: 2015/4/24
Updated in MMDB: 2015/12
Experimental Method:
x-ray diffraction
Resolution: 2.12  Å
Source Organism:
Similar Structures:
Biological Unit for 4ZH7: monomeric; determined by author and by software (PISA)
Molecular Components in 4ZH7
Label Count Molecule
Protein (1 molecule)
1
Outer Membrane Protein-adhesin
Molecule annotation
Chemicals (5 molecules)
1
2
2
2
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.