Question

Problem 11 (3 points): On the example of orotidine monophosphate decarboxylase, explain why it is very important for enzymes in your cell to be highly specific.

Answer 1

Enzymes are highly specific both in the reactions that they catalyze and in their choice of reactants, which are called substrates. An enzyme usually catalyzes a single chemical reaction or a set of closely related reactions. Side reactions leading to the wasteful formation of by-products are rare in enzyme-catalyzed reactions, in contrast with uncatalyzed ones.

Many enzymes undergo substrate-induced protein conformational changes that trap their substrates in solvent occluded protein cages, but the conformational change induced by ligand binding to Orotodine monophospahte decarboxylase(OMPDC) is incredibly complex, as required to enable the development of 22 kcal/mol of stabilizing binding interactions with the phosphodianion and ribosyl substrate fragments of orotidine monophosphate(OMP).

The binding energy from these fragments is utilized to activate OMPDC for catalysis of decarboxylation at the orotate fragment of OMP, through the creation of a tight, catalytically active, protein cage from the floppy, open, unliganded form of OMPDC. Such utilization of binding energy for ligand-driven conformational changes provides a general mechanism to obtain specificity in transition state binding.

HN HN o Nң 2-O,PO4 0 7 Со, 2-o-POP0 ОН ОН UMP Он он н OMP OMDPC-Catalyzed Decarboxylation of OMP to form UMP