A5049415568- Peroxisome Proliferator-Activated Receptors
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Click Chemistry and Applications
- Biochemical and Molecular Research
- Metabolism, Diabetes, and Cancer
- Enzyme Structure and Function
- Advanced biosensing and bioanalysis techniques
- Amino Acid Enzymes and Metabolism
- Protein Structure and Dynamics
- Signaling Pathways in Disease
- Cardiovascular Function and Risk Factors
- Peptidase Inhibition and Analysis
- Enzyme-mediated dye degradation
- Inflammatory mediators and NSAID effects
- SARS-CoV-2 and COVID-19 Research
- Microbial Community Ecology and Physiology
- Drug Transport and Resistance Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Microbial bioremediation and biosurfactants
- Microplastics and Plastic Pollution
- Bacterial Genetics and Biotechnology
- Protein Degradation and Inhibitors
- Inflammation biomarkers and pathways
- Lipid metabolism and biosynthesis
Australian National University
2021-2025
Australian Research Council
2021-2025
ARC Centre of Excellence for Innovations in Peptide and Protein Science
2021-2024
The University of Adelaide
2018-2024
Antivirals that specifically target SARS-CoV-2 are needed to control the COVID-19 pandemic. The main protease (M
Fluorine atoms are known to display scalar 19F-19F couplings in nuclear magnetic resonance (NMR) spectra when they sufficiently close space for nonbonding orbitals overlap. We show that fluorinated noncanonical amino acids positioned the hydrophobic core or on surface of a protein can be linked by through-space (TSJFF) even if 19F spins time average separated more than van der Waals distance. Using two different aromatic featuring CF3 groups, O-trifluoromethyl-tyrosine and...
Abstract Cyanopyridylalanines are non‐canonical amino acids that react with aminothiol compounds under physiological conditions in a biocompatible manner without requiring added catalyst. Here we present newly developed aminoacyl‐tRNA synthetases for genetic encoding of meta ‐ and para ‐cyanopyridylalanine to enable the site‐specific attachment wide range different functionalities. The outstanding utility cyanopyridine moiety is demonstrated by examples i) post‐translational...
Proteins produced with leucine analogues, where CH
Malachite green (MG) is used as a dye for materials such wood, cotton, and nylon, in aquaculture to prevent fungal protozoan diseases. However, it highly toxic, with carcinogenic, mutagenic, teratogenic properties, resulting bans worldwide. Despite this, MG still frequently many countries due its efficacy economy. persistent the environment so requires degradative intervention. In this work we isolated Bacillus pacificus ROC1 strain from salt flat Pakistan that had ability aerobically...
Proteins operate through ligand and solvent interactions governed by thermodynamics, yet the enthalpy-entropy trade-offs that guide their functional evolution remain poorly understood. The LacI/GalR family (LGF) of transcription factors provides a system for examining how these evolve over billions years but has seldom been studied from full thermodynamic perspective. While specificity well-studied, determinants underlying changes in is not well understood, especially proteins alter...
The enzymatic degradation of polyethylene terephthalate (PET) is a promising method advanced plastic recycling. Traditional protein engineering methods often fall short in exploring sequence space for optimal enzymes due to structural and rational design limitations. Our study addresses this by using multiplexed ancestral reconstruction (mASR) explore the evolutionary PET-degrading cutinases. With dataset 397 cutinase sequences, we created diverse library sequences. Experimental...
Inverse agonists of peroxisome proliferator activated receptor γ (PPARγ) have emerged as safer alternatives to full for their reduced side effects while still maintaining impressive insulin-sensitizing properties. To shed light on molecular mechanism, we characterized the interaction PPARγ ligand binding domain with SR10221. X-ray crystallography revealed a novel mode SR10221 in presence transcriptionally repressing corepressor peptide, resulting much greater destabilization activation...
The mono(2-hydroxyethyl) terephthalate hydrolase (MHETase) from Ideonella sakaiensis carries out the second step in enzymatic depolymerization of poly(ethylene terephthalate) (PET) plastic into monomers terephthalic acid (TPA) and ethylene glycol (EG). Despite its potential industrial environmental applications, poor recombinant expression MHETase has been an obstacle to application. To overcome this barrier, we developed assay allowing for medium-throughput quantification activity cell...
Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear central to fatty acid and glucose homeostasis. PPARγ the molecular target for type 2 diabetes mellitus (T2DM) therapeutics TZDs (thiazolidinediones), full agonists of with robust antidiabetic properties, which are confounded significant side effects. Partial PPARγ, such as INT131 (1), have displayed similar insulin-sensitizing efficacy TZDs, but lack many To probe structure–activity relationship (SAR) scaffold 1, we...
Perfluorooctanoic acid (PFOA) is a widespread environmental pollutant of the perfluoroalkyl substance (PFAS) class that extremely resistant to and metabolic degradation, leading bioaccumulation. PFOA exposure has been linked many health effects including endocrine disruption dysregulation, but our understanding molecular mechanisms resulting in these outcomes remains incomplete. One target affected by ligand regulated nuclear receptor peroxisome proliferator-activated gamma (PPARγ) which...
Abstract Malachite green (MG) is used as a dye for materials such wood, cotton, and nylon, in aquaculture to prevent fungal protozoan diseases. However, it highly toxic, with carcinogenic, mutagenic, teratogenic properties, resulting bans worldwide. Despite this, MG still frequently many countries due its efficacy economy. persistent the environment so requires degradative intervention. In this work we isolated Bacillus pacificus ROC1 strain from salt flat Pakistan that had ability...
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The stereoselective reduction of alkenes conjugated to electron-withdrawing groups by ene-reductases has been extensively applied the commercial preparation fine chemicals. Although several different enzyme families are known possess ene–reductase activity, old yellow (OYE) family most thoroughly investigated. Recently, it was shown that a subset belonging flavin/deazaflavin oxidoreductase (FDOR) superfamily exhibit enantioselectivity is generally complementary seen in OYE family. These...
Obesity and rheumatic disease are mechanistically linked via chronic inflammation. The orphan receptor TREM-1 (triggering expressed on myeloid cells-1) is a potent amplifier of proinflammatory noninfectious immune responses. Here, we show that the pan modulator SR1903 effectively blocks activation. emerged from chemical series RORγ inverse agonists, although unlike close structural analogues, it has modest agonist activity LXR weak repressive (inverse agonism) PPARγ, three receptors play...
Targeting peroxisome proliferator-activated receptor (PPAR) by synthetic compounds has been shown to elicit insulin sensitising properties in type 2 diabetics.Treatment with a class of these compounds, the thiazolidinediones (TZDs), adverse side effects such as weight gain, fluid retention, and congestive heart failure.This is due their full agonist on receptor, where number genes are upregulated beyond normal physiological levels.Lessened transactivation PPAR partial agonists proved...
ABSTRACT Periplasmic solute-binding proteins (SBPs) are key ligand recognition components of bacterial ATP-binding cassette (ABC) transporters that allow bacteria to import nutrients and metabolic precursors from the environment. SBPs comprise a large diverse family proteins, which only small number have been empirically characterized. In this work, we identify set 610 unique uncharacterized within SBP_bac_5 found in conserved operons comprising genes encoding (i) ABC transport systems (ii)...
Lanthanide ions have ideal chemical properties for catalysis, such as hard Lewis acidity, fast ligand-exchange kinetics, high coordination-number preferences and low geometric requirements coordination. As a result, many small-molecule lanthanide catalysts been described in the literature. Yet, despite ability of enzymes to catalyse highly stereoselective reactions under gentle conditions, very few lanthanoenzymes investigated. In this work, mononuclear binding europium(III) gadolinium(III)...
Periplasmic solute-binding proteins (SBPs) are key ligand recognition components of bacterial ATP-binding cassette (ABC) transporters that allow bacteria to import nutrients and metabolic precursors from the environment. SBPs comprise a large diverse family proteins, which only small number have been empirically characterized. In this work, we identify set 610 unique uncharacterized within SBP_bac_5 found in conserved operons comprising genes encoding (i) ABC transport systems (ii) putative...
Abstract Cyano-tryptophans (CN-Trp) are privileged multimodal reporters on protein structure. They similar in size to the canonical amino acid tryptophan and some of them exhibit bright fluorescence which responds sensitively changes environment. We selected aminoacyl-tRNA synthetases specific for 4-, 5-, 6-, 7-CN-Trp high-yield vivo production proteins with a single, site-specifically introduced nitrile label. The absorption maximum 4-CN-Trp is distinct from Trp, allowing selective...
Cyanotryptophans (CN‐Trp) are privileged multimodal reporters on protein structure. They similar in size to the canonical amino acid tryptophan and some of them exhibit bright fluorescence which responds sensitively changes environment. We selected aminoacyl‐tRNA synthetases specific for 4‐, 5‐, 6‐, 7‐CN‐Trp high‐yield vivo production proteins with a single, site‐specifically introduced nitrile label. The absorption maximum 4‐CN‐Trp is distinct from Trp, allowing selective excitation its...
Cyanotryptophans (CN‐Trp) are privileged multimodal reporters on protein structure. They similar in size to the canonical amino acid tryptophan and some of them exhibit bright fluorescence which responds sensitively changes environment. We selected aminoacyl‐tRNA synthetases specific for 4‐, 5‐, 6‐, 7‐CN‐Trp high‐yield vivo production proteins with a single, site‐specifically introduced nitrile label. The absorption maximum 4‐CN‐Trp is distinct from Trp, allowing selective excitation its...