10. The Siroheme-[4Fe-4S] Coupled Center
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Isabel Askenasy
Abstract
In nature, sulfur exists in a range of oxidation states and the two-electron reduced form is the most commonly found in biomolecules like the sulfur-containing amino acids cysteine and methionine, some cofactors, and polysaccharides. Sulfur is reduced through two pathways: dissimilation, where sulfite (SO2-3) is used as terminal electron acceptor; and assimilation, where sulfite is reduced to sulfide (S2-) for incorporation into biomass. The pathways are independent, but share the sulfite reductase function, in which a single enzyme reduces sulfite by six electrons to make sulfide. With few exceptions, sulfite reductases from either pathway are iron metalloenzymes with structurally diverse configurations that range from monomers to tetramers. The hallmark of sulfite reductase is its catalytic center made of an iron-containing porphyrinoid called siroheme that is covalently coupled to a [4Fe-4S] cluster through a shared cysteine ligand. The substrate evolves through a push-pull mechanism, where electron transfer is coupled to three dehydration steps. Siroheme is an isobacteriochlorin that is more readily oxidized than protoporphyin IX-derived hemes. It is synthesized from uroporphyrinogen III in three steps (methylation, a dehydrogenation, and ferrochelation) that are performed by enzymes with homology to those involved in cobalamin synthesis. Future research will need to address how the siroheme-[4Fe-4S] clusters are assembled into apo-sulfite and nitrite reductases. The chapter will discuss how environmental microbes use sulfite reductase to survive in a range of ecosystems; how atomic-resolution structures of dissimilatory and assimilatory sulfite reductases reveal their ancient homology; how the siroheme-[4Fe-4S] cluster active site catalyzes the six-electron reduction of sulfite to sulfide; and how siroheme is synthesized across diverse microrganisms.
Abstract
In nature, sulfur exists in a range of oxidation states and the two-electron reduced form is the most commonly found in biomolecules like the sulfur-containing amino acids cysteine and methionine, some cofactors, and polysaccharides. Sulfur is reduced through two pathways: dissimilation, where sulfite (SO2-3) is used as terminal electron acceptor; and assimilation, where sulfite is reduced to sulfide (S2-) for incorporation into biomass. The pathways are independent, but share the sulfite reductase function, in which a single enzyme reduces sulfite by six electrons to make sulfide. With few exceptions, sulfite reductases from either pathway are iron metalloenzymes with structurally diverse configurations that range from monomers to tetramers. The hallmark of sulfite reductase is its catalytic center made of an iron-containing porphyrinoid called siroheme that is covalently coupled to a [4Fe-4S] cluster through a shared cysteine ligand. The substrate evolves through a push-pull mechanism, where electron transfer is coupled to three dehydration steps. Siroheme is an isobacteriochlorin that is more readily oxidized than protoporphyin IX-derived hemes. It is synthesized from uroporphyrinogen III in three steps (methylation, a dehydrogenation, and ferrochelation) that are performed by enzymes with homology to those involved in cobalamin synthesis. Future research will need to address how the siroheme-[4Fe-4S] clusters are assembled into apo-sulfite and nitrite reductases. The chapter will discuss how environmental microbes use sulfite reductase to survive in a range of ecosystems; how atomic-resolution structures of dissimilatory and assimilatory sulfite reductases reveal their ancient homology; how the siroheme-[4Fe-4S] cluster active site catalyzes the six-electron reduction of sulfite to sulfide; and how siroheme is synthesized across diverse microrganisms.
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series. Metal Ions in Life Sciences* vii
- Preface to Volume 20. Transition Metals and Sulfur: A Strong Relationship for Life ix
- Contents xiii
- Contributors to Volume 20 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. Introduction: Transition Metals and Sulfur 1
- 2. Sulfur, the Versatile Non-metal 19
- 3. The Type 1 Blue Copper Site: From Electron Transfer to Biological Function 51
- 4. Purple Mixed-Valent Copper A 91
- 5. The Tetranuclear Copper-Sulfide Center of Nitrous Oxide Reductase 139
- 6. Cytochrome P450. The Dioxygen-Activating Heme Thiolate 165
- 7. Basic Iron-Sulfur Centers 199
- 8. The Cofactors of Nitrogenases 257
- 9. Molybdenum and Tungsten Cofactors and the Reactions They Catalyze 313
- 10. The Siroheme-[4Fe-4S] Coupled Center 343
- 11. Nickel, Iron, Sulfur Sites 381
- 12. Zinc Fingers 415
- SUBJECT INDEX 437
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series. Metal Ions in Life Sciences* vii
- Preface to Volume 20. Transition Metals and Sulfur: A Strong Relationship for Life ix
- Contents xiii
- Contributors to Volume 20 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. Introduction: Transition Metals and Sulfur 1
- 2. Sulfur, the Versatile Non-metal 19
- 3. The Type 1 Blue Copper Site: From Electron Transfer to Biological Function 51
- 4. Purple Mixed-Valent Copper A 91
- 5. The Tetranuclear Copper-Sulfide Center of Nitrous Oxide Reductase 139
- 6. Cytochrome P450. The Dioxygen-Activating Heme Thiolate 165
- 7. Basic Iron-Sulfur Centers 199
- 8. The Cofactors of Nitrogenases 257
- 9. Molybdenum and Tungsten Cofactors and the Reactions They Catalyze 313
- 10. The Siroheme-[4Fe-4S] Coupled Center 343
- 11. Nickel, Iron, Sulfur Sites 381
- 12. Zinc Fingers 415
- SUBJECT INDEX 437
