The small, 78-residue long, regulator SipA interacts with the non-bleaching sensor histidine kinase (NblS). We have solved the solution structure of SipA on the basis of 990 nuclear Overhauser effect- (NOE-) derived distance constraints. The average pairwise root-mean-square deviation (RMSD) for the twenty best structures for the backbone residues, obtained by CYANA, was 1.35 ± 0.21 Å, and 1.90 ± 0.16 Å when all heavy atoms were considered (the target function of CYANA was 0.540 ± 0.08). The structure is that of a β-II class protein, basically formed by a five-stranded β-sheet composed of antiparallel strands following the arrangement: Gly6-Leu11 (β-strand 1), which packs against Leu66-Val69 (β-strand 5) on one side, and against Gly36-Thr42 (β-strand 2) on the other side; Trp50-Phe54 (β-strand 3); and Gly57-Leu60 (β-strand 4). The protein is highly mobile, as shown by measurements of R1, R2, NOE and ηxy relaxation parameters, with an average order parameter (<S2>) of 0.70; this mobility encompasses movements in different time scales. We hypothesize that this high flexibility allows the interaction with other proteins (among them NblS), and it explains the large conformational stability of SipA.