The structures of α2u-globulin and its complex with a hyaline droplet inducer

alpha(2u)-Globulin (A2U) is the major urinary protein excreted by adult male rats. The structure of a monoclinic crystal form of A2U was reported in 1992 [Bocskei er al. (1992). Nature (London), 360, 186-188], The structures of an orthorhombic crystal form of A2U at 2.5 Angstrom resolution (refined to an R factor of 0.248; R-free = 0.264) and of a complex between A2U and d-limonene 1,2-epoxide (DLO) at 2.9 Angstrom resolution (R factor = 0.248; R-free = 0.260) are presented here. DLO is one of a diverse group of chemicals which cause a male rat-specific renal carcinogenesis called hyaline-droplet nephropathy. The rate-determining step in the development of this disorder is the binding of the toxin to A2U. Comparison of the cavities in A2U and in the corresponding mouse urinary protein (MUP) reveal that the former is tailor-made for small oval hydrophobic ligands such as DLO. The cavity in MUP is more shallow and elongated and cannot easily accommodate such ligands.