Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second ....Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second function of these enzymes, namely their ability to break down organophosphorus-containing insecticides and nerve agents. Ultimately, the structural information resulting from this project may be used in drug design to regulate blood pressure and in engineering proteins for bioremediation.Read moreRead less
The structure and function of dihydroorotase - an enzyme essential for pyrimidine biosynthesis. Malaria has recently re-emerged as one of the major life threatening diseases worldwide. With increasing travel and climate change, malaria is increasingly endangering Australians at home and abroad. Our work aims to provide the basis for the rational design of a new class of anti-malarial drugs by the systematic and thorough analysis of an essential enzyme in the malarial parasite.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0236372
Funder
Australian Research Council
Funding Amount
$100,000.00
Summary
CENTRIFUGATION FACILITIES FOR THE GENETICS ANALYSIS FACILITY. Access to both a high-speed centrifuge and an ultracentrifuge is essential for a wide range of biochemistry and molecular biology research projects. A high-speed centrifuge is essential for the collection of bacteria cultured to express specific proteins as well as the collection of purified proteins isolated from a wide range of organisms. Similarly an ultracentrifuge is required for the isolation of viruses and the preparation and p ....CENTRIFUGATION FACILITIES FOR THE GENETICS ANALYSIS FACILITY. Access to both a high-speed centrifuge and an ultracentrifuge is essential for a wide range of biochemistry and molecular biology research projects. A high-speed centrifuge is essential for the collection of bacteria cultured to express specific proteins as well as the collection of purified proteins isolated from a wide range of organisms. Similarly an ultracentrifuge is required for the isolation of viruses and the preparation and purification of RNA and DNA. The two machines will facilitate the continuation of research projects funded by both government and industry grants. The centrifuges will complement the equipment available in the Genetic Analysis Facility.Read moreRead less
A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crysta ....A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crystal structure of human GSTK; (4) An understanding of GSTK's substrate specificity, reaction kinetics and structure/function relationships. Since GSTK is confined to mitochondria, and may not be related to other GSTs, we may also identify novel functionsRead moreRead less
New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
Th ....New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
This project, which will use cutting edge techniques in an experimental model, seeks to characterise this important enzyme's function so that better treatments can be developed in future for diabetes and obesity.
Read moreRead less
How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive unders ....How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive understanding of the AMP activated protein kinase (enzyme isoforms, genes, physiological roles and regulation). This knowledge will have major benefits in biopharmaceutical development, the livestock, plant and sport/racing industries.Read moreRead less
Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ra ....Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ray diffraction; (ii) To use affinity-labelling to determine the amino acid residues in the binding site of the enzyme's allosteric activator, acetyl-CoA; (iii) To construct chimeric enzymes from different species to define regions of the enzyme which affect its responses to its important allosteric activator, acetyl-CoA.
Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101173
Funder
Australian Research Council
Funding Amount
$374,318.00
Summary
Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the par ....Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the parasites. Adenylate-forming enzymes play critical roles in a diverse range of biochemical pathways, such as protein translation and fatty acid metabolism. The project seeks to deliver a new paradigm for the design of future antiparasitic agents.Read moreRead less
Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology t ....Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology that will make cell-free production of recombinant proteins rapid, cheap, and scalable. This will advance Australia’s intellectual leadership in the area of biotechnology and will bring numerous economic benefits by accelerating pharmaceutical development. Read moreRead less