FAD sequestering proteins protect mycobacteria – new paper!

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In this work, recently published in the Journal of Biological Chemistry, we use a number of biochemical and structural analyses to show that a previously uncharacterised protein from Mycobacterium smegmatis acts as a flavin-sequestering protein that is required for survival during hypoxia. We show that this protein is a member of the flavin- and deazaflavin-dependent oxidoreductases (FDORs) and is distributed across mycobacterial species. X-ray crystallography revealed how FAD binds and showed no other substrate-binding cavities – consistent with its role as a flavin-sequestering protein. These findings present a new paradigm in mycobacterial adaptation to hypoxia.

This work was led by members of Greg Cook’s group (University of Otago/University of Auckland) and a collaboration with Trevor Rapson (CSIRO) and Chris Greening (Monash). Congratulations to all involved with this work.

Find the paper here. 

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Neofunctionalisation of two Drosophila esterases – new paper!

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Understanding how proteins gain new functions following gene duplication (i.e. neofunctionalisation) via structural changes is a key research theme in the Jackson group. In this paper, published recently in Insect Biochemistry and Molecular Biologywe use phylogenetic analysis, biochemical comparisons, and structural analysis to explore the evolutionary trajectories that link two Drosophila esterases.

This work was done in collaboration with members of John Oakeshott group (CSIRO). Congratulations to Davis and all those involved in this work!

Read the paper here

Structure and stability of gammaS-Crystallin sheds light on cataract formation – New paper in JMB!

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Read the paper here! 

Cataracts, the clouding of the eye lens, is a leading cause of blindness and visual impairments worldwide. Cataracts form when oxidative stress in the lens causes lens proteins, such as crystallin, to destabilise and aggregate. The molecular basis for the oxidation-induced aggregation of these proteins, however, has remained elusive. In this paper, recently published in the Journal of Molecular Biology, we use X-ray crystallography and small-angle X-ray light scattering to describe the structure of a disulfide-linked dimer of human gammaS-crystallin. This disulfide-linked dimer is prone to forming aggregates and would likely be prevalent in aging eyes. These findings provide insight into how oxidative modification of crystallins contributes to cataract formation.

This work was a collaboration with, and led by, members of the Carver Group at the Australian National University. Congratulations to all involved!

 

 

The evolution of multiple active site configurations in a designed enzyme – New Nature Communications Paper!

 

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Congratulations to Nansook and everyone involved in this project! This has been a great collaboration with Lynn Kamerlin (Uppsala University), Chris Easton (ANU) and Michelle Coote’s (ANU) groups.

In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.

https://www.nature.com/articles/s41467-018-06305-y

Postdoctoral Fellow Position in the Jackson Lab – Apply Now!

Come and work with us on an exciting, collaborative project at the Australian National University!

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The ANU Grand Challenge Research Program on Novel Miniaturized Medical Sensor Technology is now advertising Postdoctoral Fellow / Research Fellow positions located each in the Research Schools of Chemistry, Engineering, and Physics to work on the development of novel miniaturized biomedical sensors that can be integrated into wearable and point-of-care devices. These positions will work synergistically with the ANU Grand Challenge team benefitting from the breadth of the research programs and expertise. This project aims to revolutionise personalised medicine by providing new means for non-invasive collection and analysis of health data including the development of miniaturized sensors for detection of biomarkers in multiple sclerosis and diabetes.

The Research School of Chemistry Research Fellow will work in Associate Professor Colin Jackson’s group, and be responsible for design, engineering, and production of proteins as a key component of these biosensors. This could include engineering binding selectivity, optimizing ligand affinity, and chemical modification of the protein to function as part of a complex matrix, such as protein hydrogels.

For more details on how to apply, please follow this link: http://jobs.anu.edu.au/cw/en/job/526630/postdoctoral-fellow

 

 

Galen hits ‘Submit’ on his PhD Thesis!

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Congratulations to Galen Correy who submitted his PhD thesis last week! Here he is clicking on the ‘submit’ button. Well done Galen!

 

Check out a few of Galen’s papers:

 

 

 

 

Ben Clifton awarded ‘Best Thesis’

Ex-Jackson group member Dr. Ben Clifton has been awarded the ‘ANU Research School of Chemistry Director’s award for the Best Thesis 2017’. Ben’s PhD thesis ‘Functional evolution of solute-binding proteins’ describes the use of ancestral protein reconstruction to explore the molecular evolution of binding specificity and catalysis in amino-acid binding proteins.

You can find some of Ben’s published work here:

 

Congratulations Ben!