Methyl-coenzyme-M reductase (MCR) is a key enzyme common to all methane-producing pathogens. It catalyses the final step in methane synthesis. Each MCR contains two noncovalently bound molecules of cofactor F430. Normal-coordinate structural decomposition, hole-size analysis, and molecular mechanics calculations were undertaken to examine the effect of MCR on the hole-size and nonplanar deformations of coenzyme F430. In MCR, the protein prevents F430 from undergoing nonplanar deformations, which results in a more rigid tetrahydrocorphinoid cofactor that has a shorter ideal metal-nitrogen distance in the MCR protein matrix than it does in solution. Changing the coordination number of the nickel ion in F430 has a very small effect on the ideal hole size; however, it has a significant effect on the nonplanar deformations the coenzyme undergoes upon contraction and expansion. In all complexes we examined, cofactor F430 undergoes more nonplanar deformations when it contains a four-coordinate metal ion than it does when it contains a six-coordinate metal ion. Clearly, MCR moderates the hole-size and the nonplanar deformations of coenzyme F430, which are known to affect redox potentials and axial ligand affinities. This suggests that the protein environment may be responsible for tuning the chemistry of the active-site nickel ion.