Linkage isomerism in nitrite reduction by cytochrome cd1 nitrite reductase

Nitrite reduction by cytochrome cd(1) nitrite reductase (cd(1)NIR) is currently accepted to involve coordination of the nitrite nitrogen atom to the ferrous d(1) heme. Here, density functional theory results are reported on the previously unexplored O-binding of nitrite to ferrous and ferric cd(1)NIR. Although the N-isomer (nitro) is energetically favored over the O-nitrite (nitrito), even one single strong hydrogen bond may provide the energy required to put the two isomers on level terms. When hydrogen bonding existent at the cd(1)NIR active site is accounted for in the computational model, the O-nitrite isomer is found to spontaneously protonate and thus yield a ferric-hydroxo species, liberating nitric oxide. An O-nitrite ferrous cd(1)NIR complex appears to be an energetically feasible intermediate for nitrite reduction. O-Coordination would offer an advantage since the end product of nitrite reduction would be a ferric-hydroxo/water complex, rather than the more kinetically inert iron-nitrosyl complex implied by the N-nitrite mechanism.