Coupling between oxidation state and hydrogen bond conformation in high potential iron-sulfur protein.

Iron-sulfur proteins for which crystal structures are known all contain several NH .. S hydrogen bonds between backbone amide groups and sulfur atoms in the iron-sulfur cluster. Moreover, there is an approximate correlation between the number of such NH ... S hydrogen bonds in the environment of a given (CysS)4Fe4S4* cluster and its oxidation-reduction potential (Carter, C. W., Jr. (1977) J. Biol. Chem 252, 7802-7811). In high potential iron-sulfur protein (HiPIP) these hydrogen bonds shorten and/or become more linear in the reduced state of the molecule (Carter, C. W., Jr., Kraut, J., Freer, S. T., and Alden, R. A. (1974) J. Biol. Chem. 249, 6339-6346). Here we examine the possibility, implicit in these observations, that cluster oxidation states and hydrogen bond geometries may exhibit reciprocal influences, one on the other, as are characteristic of coupled equilibria. Ab initio molecular orbital calculations are employed to provide a guide to the nature of the polypeptidecluster hydrogen bond interactions and the interactions involving the invariant tyrosine residue. First, we have studied the effects of aliphatic and aromatic substituents on sulfur atoms in delocalizing negative charge, ie. lowering the total energy in the presence of added charge, and compared them with the effects of hydrogen bonding. The calculations show that both electron withdrawing groups bonded to sulfur and NH...S hydrogen bonds to sulfur can exert substantial effects in stabilizing added negative charge to the (CysS)4Fe4S4*. A test of the validity of our computations demonstrated that the calculated stability order for substituents on sulfur parallels the experimentally measured midpoint potentials ofinorganic analog clusters with these substituents. Second, dimerization energies, for hydrogen bonded dimers, obtained from calculations which model changes in oxidation state and geometry, are used to estimate the strength of NH.. .S,(Cys) and NH. --S* hydrogen bonds. Third, analysis of the relationship between Tyr 19, S*3, and NH 72 shows that the phenol ring should be more strongly attracted to both latter moieties in reduced HiPIP than in oxidized HiPIP.