Orotidine Decarboxylase

A "Proficient" Enzyme

Orotidine decarboxylase catalyzes the last step in the biosynthetic pathway leading to UMP (uridine monophosphate). It produces a 10²³ rate enhancement over the uncatalyzed reaction, as estimated by the Wolfenden group.

This is one of the largest rate enhancements in all of enzyme catalysis.

Carbamoyl Phosphate Synthetase (1a9x) ADP and Ornithine Bound (1a9x)	Aspartate Transcarbamoylase (5at1) CTP Bound

Carbamoyl phosphate synthetase consists of two subunits:

The small subunit catalyzes the hydrolysis of glutamine to glutamate and ammonia
The ammonia is passed along an internal tunnel to the large subunit, where it is reacted with bicarbonate

Tunnel in Carbamoyl Phosphate Synthetase

Dihydroorotase (1j79), Orotate (top domain) and Carbamoyl Aspartate Bound	Dihydroorotate Dehydrogenase (1d3h), Orotate and FMN Bound

Orotate Phosphoribosyl Transferase (1opr) Orotate and Phosphoribosyl Phosphate (front, right) Bound

Orotidine Decarboxylase (trimer; 1dbt), UMP Bound

In animals, the first three steps are catalyzed by a single large protein; similarly, the last two are carried out by a single enzyme
In bacteria, all six steps are individually catalyzed

This page last modified 10:35 AM on Sunday April 26th, 2009.
Webmaster, Department of Chemistry, University of Maine, Orono, ME 04469