The open reading frame ry1364c of Mycobacterium tuberculosis, which regulates the stress-dependent a factor, sigma(F), has been analyzed structurally and functionally. Rv1364c contains domains with sequence similarity to the RsbP/RsbW/RsbV regulatory system of the stress-response sigma factor of Bacillus subtilis. Rv1364c contains, sequentially, a PAS domain (which shows sequence similarity to the PAS domain of the B. subtilis RsbP protein), an active phosphatase domain, a kinase (anti-sigma(F) like) domain and a C-terminal anti-sigma(F) antagonist like domain. The crystal structures of two PAS domain constructs (at 2.3 and 1.6 angstrom) and aophosphatase/kinase dual domain construct (at 2.6 angstrom) are described. The PAS domain is shown to bind palmitic acid but to have 100 times greater affinity for palmitoleic acid. The full-length protein can exist in solution as both monomer and dimer. We speculate that a switch between monomer and dimer, possibly resulting from fatty acid binding, affects the accessibility of the serine of the C-terminal, anti-sigma(F) antagonist domain for dephosphorylation by the phosphatase domain thus indirectly altering the availability of sigma(F).