The structures of alpha(2u)-globulin and its complex with a hyaline droplet inducer

alpha(2u)-Globulin (A2U) is the major urinary protein excreted by adult mal e rats. The structure of a monoclinic crystal form of A2U was reported in 1 992 [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 chemica ls which cause a male rat-specific renal carcinogenesis called hyaline-drop let nephropathy. The rate-determining step in the development of this disor der is the binding of the toxin to A2U. Comparison of the cavities in A2U a nd in the corresponding mouse urinary protein (MUP) reveal that the former is tailor-made for small oval hydrophobic ligands such as DLO. The cavity i n MUP is more shallow and elongated and cannot easily accommodate such liga nds.