Definition of the Chemical Mechanism of the Photosynthetic Enzyme Rubisco


Principal Investigator

Jill Gready

John Curtin School of Medical Research




Rubisco (D-ribulose-1,5-bisphosphate Carboxylase/ Oxygenase) is arguably the most important enzyme
on earth. Performing the "synthesis" in photosynthesis it is responsible for fixing all but a small portion of the carbon in the biosphere. Despite extensive experimental investigation, this critical enzyme is poorly understood. The main aim of this project has been to understand the chemical mechanisms involved in the reaction catalysed by Rubisco. Several key questions define our interest. What are the roles played by several residues that have been shown to be essential for catalysis? What is the essential base that initiates the reaction by removing a proton from Rubisco's substrate, ribulose bisphosphate? What is the reason for Rubisco's poor performance, compared with other enzymes?

 William King

John Curtin School of Medical Research

John Andrews

Research School of Biological Sciences



u53 - VPP, PC




What are the results to date and the future of the work?

We have examined the first step in the reaction catalysed by Rubisco, the enolisation of ribulose bisphosphate. We have incorporated part of the substrate, the magnesium ion and its ligands into a 29-atom quantum-mechanical description of this first step. This is the first attempt in the literature at performing calculations on the complex Rubisco active site. This active-site model is based on extensive preliminary MD simulations and has been developed keeping in mind questions posed by experiment. We have shown that a previously ignored active-site group (a carbamylated lysine residue) could indeed play the role of the essential base. The lack of any other favourably positioned candidates supports this suggestion. Using a slightly larger active-site model, we have shown that a lysine residue previously thought to act as a base in the enolisation reaction, is in fact an acid. We are currently examining the next step, the addition of the gaseous substrate CO2, and how the the enzyme promotes this addition over that of the more abundant competitive inhibitor O2.

What computational techniques are used?

The quantum mechanical calculations are performed using the Gaussian 94 suite of programs and the Dalton package.


W. A. King, J. E. Gready and T. J. Andrews, Quantum Chemical Analysis of the Enolization of Ribulose Bisphosphate: The First Hurdle in the Fixation of CO2 by Rubisco, Biochemistry, 37, 1998, 15414-15422.


- Appendix A