UNASSIGNED: @entity6368 , the causative agent of the STI @entity2954 , is not preventable by vaccination and is rapidly developing resistance to antibiotics. However, the transferrin (Tf) receptor system, composed of TbpA and TbpB, is an ideal target for novel therapeutics and vaccine development. Using a 3D structure of gonococcal TbpA, we investigated two hypotheses: loop derived antibodies can interrupt ligand-receptor interactions in the native bacterium, and the loop 3 helix is a critical functional domain. Preliminary loop-derived antibodies, as well as optimized, second generation antibodies demonstrated similar modest ligand blocking effects on the gonococcal surface, but different effects in @entity526 . Mutagenesis of loop 3 helix residues was employed generating 11 mutants. We separately analyzed the mutants' abilities to: 1) bind Tf and 2) internalize Tf-bound @entity68 in the absence of the co-receptor TbpB. Single residue mutations resulted in up to 60% reduction in ligand binding and up to 85% reduction in @entity68 utilization. All strains were capable of growing on Tf as a sole @entity68 source. Interestingly, in the presence of TbpB, only a 30% reduction in Tf- @entity68 utilization was observed, indicating that the co-receptor can compensate for @entity73 . A complete deletion of the loop 3 helix eliminated TbpA's ability to bind Tf, to internalize @entity68 , and to grow using Tf as a sole @entity68 source. Our studies demonstrate that while the loop 3 helix is a key functional domain, function does not exclusively rely on any single residue.

Beyond the Crystal Structure: Insight into the Function and Vaccine Potential of TbpA expressed by XXXX .

@entity2954 :: ('MESH:D006069', 'Disease') :: ['gonorrhea'] @entity6368 :: ('485', 'Species') :: ['Neisseria gonorrhoeae'] @entity68 :: ('MESH:D007501', 'Chemical') :: ['iron'] @entity73 :: ('MESH:D003072', 'Disease') :: ['TbpA impairment'] @entity526 :: ('562', 'Species') :: ['E. coli']
@entity6368 :: (485,Species) :: ['Neisseria gonorrhoeae']
