Work

Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase

Year: 2023

Type: article

Abstract: -pyrazoledicarboxylic acid and MgPRPP to produce a C-nucleoside precursor of formycin A. The transformation catalysed by ForT is of chemical interest because it is one of only a few examples in which C-C bond formation takes place via an electrophilic substitution of a small, aromatic heterocycle. In addition, ForT is capable of discriminating between the aminopyrazoledicarboxylic acid and an analogue in which the amine is replaced by a hydroxyl group; a remarkable feat given the steric and electronic similarities of the two molecules. Here we report biophysical measurements, structural biology and quantum chemical calculations that provide a detailed molecular picture of ForT-catalysed C-C bond formation and the conformational changes that are coupled to catalysis. Our findings set the scene for employing engineered ForT variants in the biocatalytic production of novel, anti-viral C-nucleoside and C-nucleotide analogues.

Source: Open Biology

DOI: 10.1098/rsob.220287

Authors: Wenbo Li, Georgina C. Girt, Ashish Radadiya, James J. P. Stewart, Nigel G. J. Richards, James H. Naismith