The flexibility of carboxylate ligands in methane monooxygenase and ribonucleotide reductase: A density functional study

Available experimental data for the active sites of the hydroxylase compone nt of methane monooxygenase (MMOH) and the R2 subunit of ribonucleotide red uctase (R2) indicates high flexibility of the ligand environment of the iro n centers in these two metalloproteins, suggesting that carboxylate ligands may play a special role for proper enzymatic functioning. By using quantum chemical methods, here we have investigated (1) the so-called 1,2-carbosyl ate shift (i.e., shift of a bridging carboxylate ligand from mu -1,1 to mu -1,2 between two metal centers), and (2) the monodentate <-> bidentate rear rangement of terminal carboxylate ligands (bound to only one metal center), in the reduced forms of MMOH and R2. Our results show that (i) MMOH-like a nd R2-like structures, with a mu -1,1 and mu -1,2 bridged carboxylate ligan d, respectively, are energetically very close; (ii) complexes with lower co ordination numbers in the Fe-2 center are computed to be slightly more stab le than those with higher coordination numbers, and (nl) the two studied ca rboxylate shifts are easy processes, not only thermodynamically but also ki netically, with activation barriers of only a few kcal/mol. Our conclusion that the carboxylate ligands of dinuclear complexes such as MMOHred and R2( red) are very flexible is in a good agreement with the available experiment al data.