Cytochrome c nitrite reductase from Wolinella succinogenes - Structure at 1.6 angstrom resolution, inhibitor binding, and heme-packing motifs

Cytochrome c nitrite reductase catalyzes the 6-electron reduction of nitrit e to ammonia. This second part of the respiratory pathway of nitrate ammoni fication is a key step in the biological nitrogen cycle. The x-ray structur e of the enzyme from the epsilon -proteobacterium Wolinella succinogenes ha s been solved to a resolution of 1.6 Angstrom It is a pentaheme c-type cyto chrome whose heme groups are packed in characteristic motifs that also occu r in other multiheme cytochromes. Structures of W. succinogenes nitrite red uctase have been obtained with water bound to the active site heme iron as well as complexes with two inhibitors, sulfate and azide, whose binding mod es and inhibitory functions differ significantly. Cytochrome c nitrite redu ctase is part of a highly optimized respiratory system found in a wide rang e of Gram-negative bacteria. It reduces both anionic and neutral substrates at the distal side of a lysine-coordinated high-spin heme group, which is accessible through two different channels, allowing for a guided flow of re action educt and product. Based on sequence comparison and secondary struct ure prediction, we have demonstrated that cytochrome c nitrite reductases c onstitute a protein family of high structural similarity.