Empirical Force Field Analysis of the Revised Structure of Coenzyme F430. Epimerization and Geometry of the Corphinoid Tetrapyrrole

Abstract

We undertook an empirical force field analysis of the conformational changes that accompany the diepimeriztion of coenzyme F430. The crystal structure of 12,13-diepi F430M was used as a test of the parameter set and as the basis for the calculations. The individual pyrrole rings in 13-epi and 12,13-diepi F430 adopt alternating half chair conformations leading to a ruffled macrocycle, native F430 is also ruffled but the individual pyrroles are planar. The 12,13 di-dehydro F430 and native F430 conformations are extremely similar, this accounts for the experimental observation that reduction of 12,13 di-dehydro-F430 forms native F430 and not 12,13-diepi F430. Native F430 can easily accommodate both square planar and, by bending, trigonal bipyramidal coordination geometries about nickel. We suggest the bent trigonal bipyramidal form is the conformer bound to the protein and that direct binding of the amino acid side chains to nickel is probably not important.