4zh0

Structure of Helicobacter pylori adhesin BabA determined by SeMet SAD

spinqualitylabelsall models 4zh0, resolution 1.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zh0 is a 1 chain structure with sequence from Helicobacter pylori. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9ZKV2_HELPJ Publication Abstract from PubMed 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. Structural basis of Lewis antigen binding by the adhesin BabA.,Hage N, Howard T, Phillips C, Brassington C, Overman R, Debreczeni J, Gellert P, Stolnik S, Winkler GS, Falcone FH Sci Adv. 2015 Aug 14;1(7):e1500315. eCollection 2015 Aug. PMID:26601230 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adhesin 3D structures

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