More Papers in 2016

We published several papers in the second half of 2016. Below is a summary of some of these publications. Congratulations to everyone involved!

Elaaf’s paper ‘Hydrophobic shielding drives catalysis of hydride transfer in a family of F420H2-dependent enzymes’ in Biochemistry presents work done combining quantum mechanics and molecular dynamics calculations to study the catalytic mechanism of the activation of pretomanid by the deazaflavin-dependent nitroreductase (Ddn) from Mycobacterium tuberculosis.
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Josh, Jason and Will published ‘Rangefinder: a semisynthetic FRET sensor design algorithm’ in ACS Sensors describing and demonstrating the use of a computational algorithm for the rapid in silico screening of dye attachment sites for the design of FRET sensors.
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Elena’s paper ‘Active site desolvation and thermostability tradeoffs in the evolution of catalytically diverse triazine hydrolases.’ in Biochemistry presents work showing how the desolation of a reactive glutamate residue by second-shell residues and thermostability trade-offs contribute to the evolution of triazine hydrolases.
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Dongdi’s paper ‘Classification and substrate head-group specificity of membrane fatty acid desaturases.’ in Computational and Structural Biotechnology Journal presents a detailed classification membrane fatty acid desaturases with regard to their function and substrate head-group specificity. This work will aid the rapid prediction of the function and specificity of new and existing sequences within this superfamily, as well as forming a basis for future efforts to manipulate the substrate specificity of these proteins for biotechnology applications.
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Eleanor’s paper ‘The role of protein dynamics in the evolution of new enzyme function’, published in Nature Chemical Biology examines a ‘molecular fossil record’ that was recently obtained during the laboratory evolution of a phosphotriesterase from Pseudomonas diminuta to an arylesterase. This results of this work establish that changes to the conformational landscapes of proteins are an essential aspect of molecular evolution and that change in function can be achieved through enrichment of preexisting conformational sub-states.
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Blair and Hafna’s paper ‘The methanogenic redox cofactor F420 is widely synthesized by aerobic soil bacteria.’ in The ISME Journal, presents work in which the genes encoding F420 biosynthesis enzymes are detected in a wide range of bacterial and archaea species, and are disproportionally abundant in aerated soils. The data suggest that although the Fo precursor to F420 originated in methanogens, F420 itself was first synthesized in an ancestral actinobacterium.

Camilla, Ben, Joe and Colin, in collaboration with the Cockburn lab at John Curtin School of Medical Research, released a pre-print version of their paper ‘Multivalency drives the neutralizing activity of antibodies against the Plasmodium falciparum circumsporozoite protein.’ in bioRxiv. In this work, we analysed the binding of the Plasmodium-neutralizing 2A10 antibody to the Plasmodium falciparum circumsporozoite protein.
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In Thanavit, Blair, Brendon and Colin’s paper ‘The redox cofactor F420 protects mycobacteria from diverse antimicrobial compounds and mediates a reductive detoxification system’ in Applied Environmental Microbiology, we explored our hypothesis that F420 enhances persistence by serving as a cofactor in antimicrobial-detoxifying enzymes. This was work done in collaboration with CSIRO.

Nick, Galen and Colin contributed to ‘Molecular basis for the behavioral effects of the odorant degrading enzyme Esterase 6’ in Scientific Reports. This work presents a model in which esterase 6 acts as a direct odorant degrading enzyme for many bioactive food esters, but not cis-vaccenyl acetate.
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Catching up on some new & old news

The last year or so has been a big one in the Jackson lab! We have had several PhD students submit and head off of new adventures; we have welcomed new members to group; had a number of exciting papers published, and attended conferences together. However, the blog section of this page has been a bit quiet – so it’s time to catch up on some new and old news!

A Farewell Hike

Towards the end of 2016, the Jackson lab headed out to Bungonia National Park to make the most of the warmer weather. Ever efficient, the E3 team took the opportunity to catch blowflies for genomic analysis along the way.

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The hike was also a chance to say goodbye to a few Jackson lab members who were departing. PhD students Ben, Nick, Jason and Elena completed their time with the group at the end of 2016, as did honours students Jen and Janelle.

The hike into Bungonia gorge was treacherous and tiring, but the group was rewarded with a swim in an idyllic river at the bottom.

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While our resident hike-planner (Nick) has departed, there will certainly be more compulsory fun scheduled for 2017.

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Happy New Year!

New publication

Congratulations to Nansook, who published a paper in Biochemistry together with collaborators from the Tokuriki lab: “Conformational tinkering drives evolution of a promiscuous activity through indirect mutational effects”. [link]

In this work, we used laboratory evolution to effect a thousand-fold increase in phosphotriesterase activity in a lactonase enzyme. Mutations acquired during evolution altered the position of an active site residue that previously had no functional role, improving the alignment of the substrate in the active site and thereby increasing phosphotriesterase activity. This work gives a detailed picture of how “conformational tinkering” by remote mutations can allow large increases in enzyme activity.

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New Publication

Congratulations to Peter, whose paper “Sensing and signaling of oxidative stress in chloroplasts by inactivation of the SAL1 phosphoadenosine phosphatase” was published in PNAS [link]. This work was done with a number of collaborators, including the Pogson group at the ANU Research School of Biology.

When adverse conditions like drought cause oxidative stress in plant chloroplasts, a chemical messenger originating from the chloroplast induces a stress response in the plant. Our work shows how oxidative stress is detected and converted to this chemical stress signal: oxidative stress inactivates the enzyme that eliminates the stress signal, allowing it to accumulate.

Pete and Kai explain the potential applications for drought resistance in crops:

New publication

Congratulations to Hafna, Elaaf and Brendon, whose paper “Rv2074 is a novel F420H2-dependent biliverdin reductase in Mycobacterium tuberculosis” was published in Protein Science. [link]

In this work, we identified and characterised a biliverdin reductase from Mycobacterium tuberculosis, and elucidated its catalytic mechanism. This enzyme produces a potent antioxidant, bilirubin, using biliverdin, which is produced in large amounts in macrophages infected with mycobacteria. Thus, biliverdin reductase could contribute to the persistence of M. tuberculosis in macrophages (the cause of latent tuberculosis infection) by protecting the bacterium from oxidative stress.

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