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 | Research Interests |  |
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| Protein Structure and Protein Interactions |
| | We have focused on two of our projects from 2002 highlighting how protein structure aids understanding of protein interactions and protein function.
Sulfotransferases play an important role in chemical defense against xenobiotics but can also bioactivate carcinogens.
We determined the structure of a major human sulfotransferase, SULT1A1, in collaboration with Professor Mick McManus (UQ).
Unexpectedly, the structure shows two molecules of the substrate p-nitrophenol at the active site and suggests that the active site can adapt its architecture to accept hydrophobic substrates of varying sizes, shapes and flexibility.
Thus the crystal structure provides the molecular basis for substrate inhibition of SULT1A1 and reveals clues as to how the enzyme sulfonates a wide variety of lipophilic compounds.
The second example is that of DsbE, now also known as CcmG. This is one of a family of Dsb proteins that play a critical role in cellular redox control and assists in the folding and function of many proteins, including toxins and virulence factors.
Amid the highly oxidizing environment of the periplasm, there is a need for selected protein cysteines to be kept in a reduced form. Thus the protein CcmG (DsbE) is necessary to keep apocytochrome C in the reduced form.
Unlike other periplasmic thioredoxin-like proteins, CcmG has a specific reducing activity in the highly oxidizing periplasmic environment and has a high fidelity of interaction.
In collaboration with Dr Linda Thöny-Meyer from ETH-Zürich we determined the structure of CcmG, showing it to incorporate a modified thioredoxin fold with an acidic active site and a groove formed from two inserts. Both these structural features are necessary for CcmG function. |
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