THE COORDINATION CHEMISTRY OF THE STRUCTURAL ZINC ION IN ALCOHOL-DEHYDROGENASE STUDIED BY AB-INITIO QUANTUM-CHEMICAL CALCULATIONS

The coordination chemistry of the structural zinc ion in horse liver a lcohol dehydrogenase has been examined by quantum chemical geometry op timisations. It is shown that all four cysteine ligands are deprotonat ed in the enzyme, not only two of them as has been suggested. The Zn-S bond lengths are very sensitive to the theoretical treatment; in vacu um they are predicted to be 15 pm longer than in the crystal structure . Half of this discrepancy is due to electronic correlation, the rest can be attributed to screening of the negative sulphide charges by the enzyme, in particular by N-H ... S hydrogen bonds. The potential surf ace is rather flat, so the large difference in geometry between the cr ystal and the vacuum structure corresponds to an energy change of less than 35 kJ/mol. The experimental bond lengths can be reproduced only with methods that account explicitly for the enzyme. A dielectric cont inuum model gives bond lengths which are too long, indicating that the enzyme solvates the coordination sphere better than water. Thus, the structural zinc ion can be used as a sensitive test of methods which t ry to model the surrounding medium in quantum chemical computations.