Spin-dependent mechanism for diatomic ligand binding to heme

Abstract

The nature of diatomic ligand recombination in heme proteins is elucidated by using a Landau-Zener model for the electronic coupling in the recombination rate constant. The model is developed by means of explicit potential energy surfaces calculated by using density functional theory (DFT). The interaction of all possible spin states of the three common diatomic ligands, CO, NO, and O2, and high-spin heme iron is compared. The electronic coupling, rebinding barrier, and Landau-Zener force terms can be obtained and used to demonstrate significant differences among the ligands. In particular the intermediate spin states of NO (S ‫؍‬ 3͞2) and O2 (S ‫؍‬ 1) are shown to be bound states. Rapid recombination occurs from these bound states in agreement with experimental data. The slower phases of O2 recombination can be explained by the presence of two higher spin states, S ‫؍‬ 2 and S ‫؍‬ 3, which have a small and relatively large barrier to ligand recombination, respectively. By contrast, the intermediate spin state for CO is not a bound state, and the only recombination pathway for CO involves direct recombination from the S ‫؍‬ 2 state. This process is significantly slower according to the Landau-Zener model. Quantitative estimates of the parameters used in the rate constants provide a complete description that explains rebinding rates that range from femtoseconds to milliseconds at ambient temperature.T he binding of diatomic ligands to heme has been studied for over 100 years (1). The dissociation of carbon monoxide (CO), nitric oxide (NO), and oxygen (O 2 ) from the iron of heme occurs by both a thermal and photolytic process (2-4). In the case of flash photolysis, the fate of the ligand depends on the competition between the intrinsic (or geminate) recombination rate constant and protein relaxation in a docking site roughly 3.5 Å from the iron as well as ligand escape from the protein (5-8). Recombination of these ligands occurs by the reverse of the thermal process. The time dependence of recombination serves as a probe of the intrinsic properties of the diatomic ligand-iron bond formation and dynamic processes that occur in the protein that surrounds the heme cofactor (9-11). The startlingly different recombination dynamics of CO, NO, and O 2 have been attributed to spin states in earlier work (3,12). In the present study, the ground state potential energy surfaces for the potential energy surfaces of all possible spin states are calculated by using density functional theory (DFT) and compared within the context of a Landau-Zener (L-Z) model for the intrinsic recombination process of each of the ligands. The observed recombination kinetics of CO, NO, and O 2 can be influenced by protein dynamics if the intrinsic recombination rate constant is slower than these dynamics (10,(13)(14)(15)(16). When a combination of temperature and viscosity dependence is used, the general time scale for the intrinsic rate constants can be extracted, and it is these rate constants that are compared in the present work.The rebindin...

How O2 Binds to Heme

“…The different relative rates for the rebinding of NO, CO, and O 2 to heme have recently been studied by DFT (16). That study also used a Landau-Zener formalism to explain the importance of spin states for the rates of ligand binding.…”

Ligand Dynamics in an Electron Transfer Protein

“…General Ligand Rebinding Properties-In general, recombination of CO with ferrous heme is slower than for O 2 and NO, presumably predominantly because of the difference in electronic interaction between the diatomic ligands and heme (44). Ligand rebinding in cyt.…”

Dynamics of Methionine Ligand Rebinding in Cytochrome c

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