2brr: Difference between revisions

In various western countries, subtype P1.4 of Neisseria meningitidis, serogroup B causes the greatest incidence of meningococcal disease. To, investigate the molecular recognition of this subtype, we crystallised a, peptide (P1HVVVNNKVATH(P11)), corresponding to the subtype P1.4 epitope, sequence of outer membrane protein PorA, in complex with a Fab fragment of, the bactericidal antibody MN20B9.34 directed against this epitope., Structure determination at 1.95 A resolution revealed a unique complex of, one P1.4 antigen peptide bound to two identical Fab fragments. One Fab, recognises the putative epitope residues in a 2:2 type I beta-turn at, residues P5NNKV(P8), whereas the other Fab binds the C-terminal residues, of the peptide that we consider a crystallisation artefact. Interestingly, recognition of the P1.4 epitope peptide is mediated almost exclusively, through the complementarity-determining regions of the heavy chain. We, exploited the observed turn conformation for designing conformationally, restricted cyclic peptides for use as a peptide vaccine. The, conformational stability of the two peptide designs was assessed by, molecular dynamics simulations. Unlike the linear peptide, both cyclic, peptides, conjugated to tetanus toxoid as a carrier protein, elicited, antibody responses in mice that recognised meningococci of subtype, P1.7-2,4. Serum bactericidal assays showed that some, but not all, of the, sera induced with the cyclic peptide conjugates could activate the, complement system with titres that were very high compared to the titres, induced by complete PorA protein in its native conformation administered, in outer membrane vesicles.

2BRR is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4, NH2 and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BRR OCA].  

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