Definition of the Chemical Mechanism of the Photosynthetic Enzyme Rubisco


Principal Investigator

Jill Gready

Division of Biochemistry and Molecular Biology,

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

Peter Cummins

John Andrews

Division of Biochemistry and Molecular Biology,

John Curtin School of Medical Research & 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 constructing a larger model of the active site to investigate the rest of the reaction, specifically focusing on the reasons for the poor substrate specificity of Rubisco.

What computational techniques are used?

The quantum mechanical calculations have been performed using the Gaussian 94 suite of programs.

Appendix A -