Refined structure of rat Clara cell 17 kDa protein at 3·0 Å resolution

The rat Clara cell 17 kDa protein (previously referred to as the rat Clara cell 10 kDa protein) has been reported to inhibit phospholipase A₂ and papain, and to also bind progesterone. It has been isolated from rat lung lavage fluid and crystallized in the space group P6₅22. The structure has been determined to 3·0 Å resolution using the molecular replacement method. Uteroglobin, whose amino acid sequence is 55·7% identical, was used as the search model. The structure was then refined using restrained least-squares and simulated annealing methods. The R-factor is 22·5%. The protein is a covalently bound dimer. Two disulfide bonds join the monomers together in an antiparallel manner such that the dimer encloses a large internal hydrophobic cavity. The hydrophobic cavity is large enough to serve as the progesterone binding site, but access to the cavity is limited. Each monomer is composed of four α-helices. The main-chain structure of the Clara cell protein closely resembles that of uteroglobin, but the nature of many of the exposed side-chains differ. This is true, particularly in a hypervariable region between residues 23 and 36, and in the H1H4 pocket.