Elucidating the behavior of an enzyme

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From the human R160Q studies, it was found that the IET rate constant decreased from 411 s) could be obtained with an R160K substitution (22).Thus, the positive charge at this location in the HSO active site is important for facilitating IET (15, 22).HSO deficiency is a rare recessive metabolic neurologic disorder that presents shortly after birth (9, 10).The disease is characterized by seizures, dislocated ocular lenses, neuropathogenesis, and early death most likely due to a combined effect of the accumulation of toxic sulfite and glutamate, decreased sulfate concentration, and oxidative stress (9, 11, 12, 13, 14).The closest approach of the two cofactors (8.5 Å) occurs between the molybdenum atom and propionate-6 of the heme and is well within typical distances for rapid electron tunneling in proteins (20).Others have emphasized that optimum electronic coupling pathways between the redox sites can be often be identified within the protein structure (21). One pathway involves Arg55 and the hydrogen bonding network to the heme propionate groups, which are directly between the two redox centers.1) and have nearly identical active site geometries that contain several conserved residues, including Cys104, Tyr236, His57, and Arg55 (SDH numbering) (6, 7, 8).

This suggests that there is no significant subunit movement or a subunit “docking” step in SDH that could be retarded by a viscogen (18, 19), and that IET occurs through the protein and/or solvent interface between the two “locked” subunits which have a Mo···Fe distance of ~16 Å (7).

All reported sulfite-oxidizing enzymes have a conserved arginine in their active site which hydrogen bonds to the equatorial oxygen ligand on the Mo atom.

Previous studies on the pathogenic R160Q mutant of human sulfite oxidase (HSO) have shown that Mo-heme intramolecular electron transfer (IET) is dramatically slowed when positive charge is lost at this position.

Sulfite dehydrogenase (SDH), isolated from the soil bacterium with thiosulfate as an energy source (4, 5).

Despite playing different metabolic roles, both SO and SDH catalyze identical chemical reactions (Eq.

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