Evidence of carbamoylphosphate induced conformational changes upon bindingto human ornithine carbamoyltransferase

Human liver ornithine carbamoyltransferase undergoes absorbance changes in the UV region upon formation of the carbamoylphosphate-norvaline-enzyme ter nary complex, The UV changes are similar in the presence of carbamoylphosph ate alone, whilst they are lower in the presence of ornithine or norvaline alone, The extent of the UV changes correlates with the enzyme susceptibili ty to proteolytic degradation, The free native enzyme is completely and rap idly hydrolyzed by trypsin, whilst it is partially protected upon carbamoyl phosphate binding, The extent of protection increases for the carbamoylphos phate-norvaline-enzyme ternary complex, These results strongly suggest that the binding of the first substrate, i.e. carbamoylphosphate, to human orni thine carbamoyltransferase induces a large protein isomerization, which reg ards the polar domain plus a part of equatorial domain of each subunit.