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An essential step in the biogeochemical cycling of sulfur is the six electron reduction of sulfite (SO32-) to sulfide (S2-) catalyzed by the enzyme sulfite reductase (SiR). SiR performs the largest single atom reduction in any biological pathway with the exception of the analogous six electron reduction of nitrite to ammonia. The reduction of SO32- to S2- is critical to the dissimilatory anaerobic respiration pathway in sulfate-reducing bacteria and assimilatory pathway responsible for incorporation of sulfur into biomolecules in plants, bacteria, and archaea. This project has successfully used mutational analysis of assimilatory sulfite reductase hemoprotein (SiRHP) to reveal a proton coupled electron transfer mechanism with nonredundant proton donors at several step of catalysis. Four hypothesized proton donors (R83, R153, K215, and K217) were independently mutated to serine, resulting in changes in substrate binding, the dynamics of an active site loop, and the number of electrons transferred per sulfur reduced. A fifth mutation was made (N149W) in an attempt to mimic an inactive siroheme site observed in the dissimilatory pathway SiR. This mutation resulted in changes in active site loop dynamics and protease sensitivity, but enhanced, rather than inhibited, the activity of the enzyme. Crystal structures were determined of the R153S variant in the oxidized state and of the N149W variant in the oxidized and reduced substrate bound state. Finally, newer work exploring an active heterodimeric form of SiR (SiRHF) is discussed. A proposal for future experiments with SiRHF is included.