Oxygen cleavage with manganese and iron in ribonucleotide reductase from Chlamydia trachomatis.

The oxygen cleavage in Chlamydia trachomatis ribonucleotide reductase (RNR) has been studied using B3LYP* hybrid density functional theory. Class Ic C. trachomatis RNR lacks the radical-bearing tyrosine, crucial for activity in conventional class I (subclass a and b) RNR. Instead of the Fe(III)Fe(III)-Tyr(rad) active state, C. trachomatis RNR has a mixed Mn(IV)Fe(III) metal center in subunit II (R2). A mixed MnFe metal center has never been observed as a radical cofactor before. The active state is generated by reductive oxygen cleavage at the metal site. On the basis of calculated barriers for oxygen cleavage in C. trachomatis R2 and R2 from Escherichia coli with a diiron, a mixed manganese-iron, and a dimanganese center, conclusions can be drawn about the effect of changing metals in R2. The oxygen cleavage is found to be governed by two factors: the redox potentials of the metals and the relative stability of the different peroxides. Mn(IV) has higher stability than Fe(IV), and the barrier is therefore lower with a mixed metal center than with a diiron center. With a dimanganese center, an asymmetric peroxide is more stable than the symmetric peroxide, and the barrier therefore becomes too high. Calculated proton-coupled redox potentials are compared to identify three possible R2 active states, the Fe(III)Fe(III)-Tyr(rad) state, the Mn(IV)Fe(III) state, and the Mn(IV)Mn(IV) state. A tentative energy profile of the thermodynamics of the radical transfer from R2 to subunit I is constructed to illustrate how the stability of the active states can be understood from a thermodynamical point of view.