Structural highlights
Publication Abstract from PubMedWith an increase in antibiotic-resistant strains, the nosocomial pathogen Acinetobacter baumannii has become a serious threat to global health. Glycoconjugate vaccines containing fragments of bacterial exopolysaccharide (EPS) are an emerging therapeutic to combat bacterial infection. Herein, we characterize the bacteriophage PhiAB6 tailspike protein (TSP), which specifically hydrolyzed the EPS of A. baumannii strain 54149 (Ab-54149). Ab-54149 EPS exhibited the same chemical structure as two antibiotic-resistant A. baumannii strains. The PhiAB6 TSP-digested products comprised oligosaccharides of two repeat units, typically with stoichiometric pseudaminic acid (Pse). The 1.48-1.89-A resolution crystal structures of an N-terminally-truncated PhiAB6 TSP and its complexes with the semi-hydrolyzed products revealed a trimeric beta-helix architecture that bears intersubunit carbohydrate-binding grooves, with some features unusual to the TSP family. The structures suggest that Pse in the substrate is an important recognition site for PhiAB6 TSP. A region in the carbohydrate-binding groove is identified as the determinant of product specificity. The structures also elucidated a retaining mechanism, for which the catalytic residues were verified by site-directed mutagenesis. Our findings provide a structural basis for engineering the enzyme to produce desired oligosaccharides, which is useful for the development of glycoconjugate vaccines against A. baumannii infection. Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage PhiAB6 tailspike protein.,Lee IM, Tu IF, Yang FL, Ko TP, Liao JH, Lin NT, Wu CY, Ren CT, Wang AH, Chang CM, Huang KF, Wu SH Sci Rep. 2017 Feb 17;7:42711. doi: 10.1038/srep42711. PMID:28209973[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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