New publication

Congratulations to Galen and the E3 team whose paper “Mapping the accessible conformational landscape of an insect carboxylesterase using conformational ensemble analysis and kinetic crystallography” has been published in Structure.

Using automated multi-conformer modelling and ensemble refinement, we uncovered a dynamically coupled network important for catalysis in an organophosphate-degrading enzyme, and using kinetic crystallography, we could monitor the release of a covalently bound intermediate in “slow motion”. This work shows how crystallographic tools can be used to explore the conformational landscape of an enzyme at each step in a complex catalytic cycle.


New publication

Congratulations to Chris, Hafna, Elaaf and Brendon, whose review “Physiology, biochemistry, and applications of F420- and Fo-dependent redox reactions” was published in Microbiology and Molecular Biology Reviews. The cover highlights some of the proteins that depend on the unique deazaflavin cofactor F420.

MMBR cover

New publication

Congratulations to Conor, whose paper “Phosphorescent oxygen-sensing and singlet oxygen production by a biosynthetic silk” was published in RSC Advances.

This work shows that porphyrin-based macrocycles can be incorporated into honeybee silk proteins. These functionalised silk films combine the useful properties of the macrocycles, such as their ability to produce antimicrobial singlet oxygen when exposed to light, with the useful properties of honeybee silk films, such as biocompatibility and stability. These materials have potential biomedical applications, in antimicrobial wound dressings, for example.


New publication

Congratulations to Nick, Peter, and Galen, whose paper “Evolution of protein quaternary structure in response to selective pressure for increased thermostability” has been published in JMB.

This paper shows that when directed evolution was used to impose selective pressure for increased thermostability in an insect carboxylesterase, stabilization was achieved by enrichment of more stable oligomeric species. This result supports the hypothesis that oligomerization is one possible evolutionary strategy for improving protein thermostability.


New publication

Congratulations to Peter, Galen and Nick, whose paper “Conformational disorganization within the active site of a recently evolved organophosphate hydrolase limits its catalytic efficiency” was published in Biochemistry.

In this paper, we characterised a gain-of-function substitution in an enzyme, which provides resistance to organophosphate pesticides in the Australian sheep blowfly. The full catalytic potential of this substitution is not realised because of frequent sampling of conformational states that are unproductive for catalysis. This may be a common feature of recently-evolved enzymes.


New publication

Congratulations to Hafna and Elaaf, whose paper “Protonation state of F420H2 in the prodrug-activating deazaflavin dependent nitroreductase (Ddn) from Mycobacterium tuberculosis” was published in Molecular BioSystems.

We identified the protonation state of the cofactor of Ddn, which is important for understanding the mechanism by which this enzyme activates anti-mycobacterial prodrugs.

molbiosyst abstract

New publication

Congratulations to Ben, whose paper “Ancestral protein reconstruction yields insights into adaptive evolution of binding specificity in solute-binding proteins” has been published in Cell Chemical Biology.

This paper gives a new structural and thermodynamic perspective on the evolution of binding specificity and shows the role of conformational plasticity and enthalpic interactions for promiscuous binding in an ancestral solute-binding protein.

BC graph abstract