Structural Biology Dr Aaron Oakley

We examine the three-dimensional structures of important biological molecules in order to understand how they work. The investigation of biological processes at the molecular level is the subject of intense interest nationally and internationally, and has applications in medicine, industrial chemistry and drug design. X-ray crystallography is used to extract detailed structural information at the atomic level for the biological molecules of interest. This can be used to see how a protein interacts with DNA, or how a drug binds to its target.

We seek to understand such diverse processes as enzyme catalysis, DNA replication and carbohydrate processing.

Current research activities

Biological detoxification

Enzymes have the potential to be used in the clean up of contaminated industrial sites. We are investigating one such enzyme, called LinB, which is capable of rendering halogenated organic compounds harmless. We have determined the structure of this enzyme at atomic resolution and are using this information to understand how the specificity of the enzyme might be modified.

Mosquitos are responsible for infecting millions of people with malaria every year. A detoxification enzyme from mosquitos, called GST, is capable of breaking down pesticides such as DDT. As such, it is involved in mosquito resistance to the pesticides. We aim to understand how the enzyme breaks down DDT and other pesticides, and how this might be applied to circumventing pesticide resistance.

Carbohydrate Chemistry

Mannan is a carbohydrate found in the flesh of ripening fruit. Control of the ripening process is important for prevention of spoilage of produce in handling and transport. We have determined the structure of an enzyme from tomato called mannanase, which breaks down mannan and helps facilitate the ripening process. We are currently working to understand how mannan is bound in the active site of the enzyme and the structural basis for substrate specificity.

DNA replication proteins

Understanding DNA replication is of fundamental importance to biology. Replication of DNA in bacteria involves an ensemble of proteins called the replisome that must work together to achieve efficient duplication of DNA molecules. We are examining some of the components of the DNA replication system. Recently, we solved the structure of a protein called DnaG C-terminal domain, which has a role in maintaining the structural integrity of the replisome.

Annual Research Report   (PDF format)

Group members

Academic Staff:
Dr Aaron J Oakley (Leader)

PhD Students:
Paul Lloyd

Key publications

1. Oakley AJ, Rossjohn J, Lo Bello M, Caccuri AM, Federici G, Parker MW. The three dimensional structure of the human pi class glutathione transferase Pl-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate. Biochemistry 36:576-585 (1997).
2. Oakley AJ, Lo Bello M, Battistoni A, Rici G, Rossjohn J, Villar H, Parker MW. The structures of human glutathione transferase Pl-1 in complex with glutathione and various inhibitors at high resolution. J Mol Biol 274:84-100 (1997).
3. Oakley AJ, Harnnoi T, Udomsinprasert R, Jirajaroenrat K, Ketterman AJ, Wilce MC. The crystal structures of glutathione S-transferases isozymes 1-3 and 1-4 from Anopheles dirus species B. Protein Sci 10:2176-85 (2001).
4. Oakley AJ, Prokop Z, Bohac M, Kmunicek J, Jedlicka T, Monincova M, Kuta-Smatanova I, Nagata Y, Damborsky J, Wilce MCJ. Exploring the structure and activity of haloalkane dehalogenase from Sphingomonas paucimobilis UT26: evidence for product- and water-mediated inhibition. Biochemistry 41:4847-4855 (2002).
5. Oakley AJ, Klvana M, Otyepka M, Nagata Y, Wilce MCJ, Damborsky J. Crystal Structure of Haloalkane Dehalogenase LinB from Sphingomonas paucimobilis UT26 at 0.95 Å Resolution: Dynamics of Catalytic Residues. Biochemistry (2004) In Press.

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group photos

Dr A J Oakley Research School of Chemistry, Building 35 Australian National University Canberra ACT 0200 AUSTRALIA Ph: +61 2 6125 8325 Fx: +61 2 6125 0750 E-mail: oakley@rsc.anu.edu.au