Cadmium-substituted alcohol dehydrogenase

Together with Lars Hemmingsen from Copenhagen, I developed a procedure for the calculation of electric field gradients of cadmium complexes [18]. This method was then used to interpret measurements performed by perturbed angular correlation of gamma-rays (PAC) on alcohol dehydrogenase [24]. Structures of the Cd-substitued enzyme with various ligands and coenzymes were estimated with COMQUM and field gradients were calculated by our method. The results are impressive: the calculations reproduce electric field gradients of seven measurements with an average error of only 0.11 a.u. (9 %), and we reinterpret several of the experiments. The results show that the enzyme is four-coordinate in all examined complex and that the measurements most likely give the first experimental evidence for Glu-68 coordinating to the cadmium ion. Such a coordination has now been confirmed by the crystal structure of human alcohol dehydrogenase [J. Mol. Biol. 265(97)330], another encouraging success for our COMQUM calculations. The calculations also indicated that the semiempirical method normally used for the interpretation of PAC measurements could be improved. We have therefore also suggested how the method may be improved using quantum chemical calibrations [35].