Moderating Influence of Proteins on Nonplanar Tetrapyrrole Deformations: Coenzyme F430 in Methyl-Coenzyme-M Reductase

Abstract

Normal-coordinate structural decomposition, cluster analysis, and molecular mechanics calculations were undertaken to examine the effect of methyl-coenzyme-M reductase (MCR) on the nonplanar deformations of coenzyme F430. Although free 12,13-diepi-F430 has a lower energy conformation than free F430, the protein restraints exerted by MCR are responsible for F430 having a lower energy conformation than the 12,13-diepimer in MCR. According to the NSD analysis, the crystal structure of free diepimerized F430M is highly distorted. In MCR the protein prevents 12,13-diepi-F430 from undergoing nonplanar deformations; therefore, MCR favors F430 over the 12,13-diepimeric form. The strain imposed on 12,13-diepi-F430 in the protein is so large that although 88% of free F430 is found in the diepimeric form, none of the diepimeric form is found in MCR. This is of significance since the two forms have different chemistries. MCR also moderates the nonplanar deformations of coenzyme F430, which are known to affect redox potentials and axial ligand affinities in tetrapyrroles, suggesting that the protein environment (MCR) is responsible for tuning the chemistry of the active site nickel ion. F430 is bound to MCR by hydrogen bonds between the protein and the F430 carboxylate groups. Conformational searches have shown that F430 has very little rotational and translational freedom within MCR.