How do new enzymes evolve from proteins that were initially specialised for binding? In this work, we use ancestral protein reconstruction to calculate and characterise the evolutionary intermediate states linking an ancestral solute-binding protein to the extant enzyme cyclohexadienyl dehydratase. We show how the intrinsic reactivity of a desolvated general acid was harnessed by a series of mutations radiating from the active site, which optimized enzyme–substrate complementarity and transition-state stabilization and minimized sampling of noncatalytic conformations.
Congratulations to Hafna, who was recently awarded an ASBMB Fellowship. These fellowships are awarded in recognition of outstanding work in the field of biochemistry and molecular biology. Well done Hafna!
The group had a great time down at the Lorne Protein Conference last week. So much great science, and an absolutely beautiful location! Matt S, Vanessa, Galen and Joe presented posters on their work. Congratulations to Galen and Joe for picking up poster prizes! Top work guys.
The week was topped off with a fabulous day at the Lorne Protein Engineering Satellite Conference which was held at the Florey Institute of Neuroscience and Mental Health, Melbourne. So much exciting work happening in the field!
We are very happy to welcome Dr Matthew Wilding to our group. Matt obtained his Ph.D. from the University of Manchester (UK) in 2012 and moved to Australia to take up a postdoctoral research position at the Commonwealth Scientific and Industrial Research Organisation (CSIRO). He was subsequently appointed as a Research Scientist at CSIRO, working in the CSIRO Biocatalysis Team. Matt has recently taken up a joint appointment between CSIRO and ANU as a Synthetic Biology Research Fellow, based at the Research School of Chemistry. Matt is (amongst many other things) currently aiming to re-engineer the translation machinery of E. coli to develop a high-throughput screen for peptide translation.
You can read more about Matt and find a list of his projects and publications here:
Check out our latest review on the laboratory evolution of protein conformational dynamics, published in Current Opinion in Structural Biology. This review focuses on recent work that has begun to establish specific functional roles for protein conformational dynamics, specifically how the conformational landscapes that proteins can sample can evolve under laboratory-based evolutionary selection. We discuss recent technical advances in computational and biophysical chemistry, which have provided us with new ways to dissect evolutionary processes. Finally, we offer some perspectives on the emerging view of conformational dynamics and evolution, and the challenges that we face in rationally engineering conformational dynamics.
Massive congratulations to our three Honours students that graduated this week – Matt, Vanessa and Paul (not pictured)! These three have worked extremely hard throughout the year and can be very proud of the work that they have done. Well done!
A molecular understanding of pesticide sequestration by insect carboxylesterases could guide the design of inhibitors to help circumvent carboxylesterase-mediated metabolic resistance to organophosphate and carbamate insecticides in insect disease vectors, such as the mosquito.
We welcome Tiffany Chau to the group! Tiffany is starting her Honours year and will be co-supervised by Professor Thomas Huber. She will be continuing the work done by Jules Kirk on EF-Tu (elongation factor thermo unstable), a prokaryotic elongation factor responsible for catalysing the binding of an aminoacyl-tRNA to the ribosome. Welcome Tiffany!
Hafna recently attended the 19th International Symposium on Flavins and Flavoproteins held in Groningen in the Netherlands. This is the largest and most specialised conference held in the field of flavin research and has been held triennially for the last 60 years. Hafna presented the work she did during her PhD on F420 binding proteins among the flavin/deazaflavin dependent oxidoreductases, and was presented with the Vince Massey Award for young investigators who have shown an outstanding contribution to the field of flavins and flavoenzymes. Top work Hafna!!