High Resolution EPR Spectroscopy - A Tool for Determining Electronic and Geometric Structure of Metalloenzymes. High resolution orientation selective pulsed EPR and END(T)OR in conjunction with computer simulation (XSophe) and computational chemistry will allow the determination of the electronic and geometric structure (distance and orientation of nuclei surrounding the metal ion(s)) of multiple redox centres in DMSOR, DorC and DMSDH to be determined. In addition pulsed ELDOR in conjunction wi ....High Resolution EPR Spectroscopy - A Tool for Determining Electronic and Geometric Structure of Metalloenzymes. High resolution orientation selective pulsed EPR and END(T)OR in conjunction with computer simulation (XSophe) and computational chemistry will allow the determination of the electronic and geometric structure (distance and orientation of nuclei surrounding the metal ion(s)) of multiple redox centres in DMSOR, DorC and DMSDH to be determined. In addition pulsed ELDOR in conjunction with molecular modelling will enable the mapping (distance and orientation) of redox centres in complex multicentered metalloproteins (DMSDH and DorC) and in protein-protein complexes (DMSOR-DorC) providing information on the pathway of electron transfer and hence the role of the pyranopterins.Read moreRead less
Special Research Initiatives - Grant ID: SR0354751
Funder
Australian Research Council
Funding Amount
$10,000.00
Summary
Australian Bio-Metals Research Network. The aim of the Bio-Metals Research Network is to connect the extensive Australian expertise in the study of metal ions in relation to the Environment, Health and Frontier Technologies. The Network is inter-disciplinary and brings together over 50 group leaders in the biological, biomedical and physical sciences. A major aim of the Network will be to provide a molecular understanding of biological and environmental processes and disease states as well as pr ....Australian Bio-Metals Research Network. The aim of the Bio-Metals Research Network is to connect the extensive Australian expertise in the study of metal ions in relation to the Environment, Health and Frontier Technologies. The Network is inter-disciplinary and brings together over 50 group leaders in the biological, biomedical and physical sciences. A major aim of the Network will be to provide a molecular understanding of biological and environmental processes and disease states as well as providing new materials for the development of new technologies. The Network will interact in research and education with Bio-Metals groups around the world and will develop collaborative funding proposalsRead moreRead less
Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possib ....Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possible when disturbances of copper metabolism become pathological. The chemistry of key molecules will be studied to reveal their essential properties and thereby to understand the molecular basis of the copper-linked diseases.Read moreRead less
Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative disea ....Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative diseases such as Alzheimer and Creutzfeldt-Jakob (mad cow). This project will study the chemistry of metabolic pathways responsible for import of nutrient copper and other metals into biological cells.Read moreRead less
Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are relat ....Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are related to the properties of the enzymes themselves or the ways in which their experiments have been conducted.Read moreRead less
Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the a ....Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the area of the Research Priority Goal: Breakthrough Science. Postgraduate research students will be trained in sophisticated state-of-the-art theoretical and synthetic chemical methodologies. The project will enhance Australia's research capability in biological (inorganic) chemistry and promote Australia's standing in the International research community.Read moreRead less
Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has ....Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has potential application in biosensors and biocatalysis.Read moreRead less
Structural studies of catalysis and electron transfer by copper proteins. We propose to determine the crystal structures of five copper-containing proteins. Three are amine oxidases, enzymes that protect a wide range of organisms against toxic cell products (amines). Novel chemical modifications and crystallographic techniques will be used to test hypotheses for the enzyme mechanism. The results will provide a basis for the future manipulation of the enzymes' activities. Our other targets, s ....Structural studies of catalysis and electron transfer by copper proteins. We propose to determine the crystal structures of five copper-containing proteins. Three are amine oxidases, enzymes that protect a wide range of organisms against toxic cell products (amines). Novel chemical modifications and crystallographic techniques will be used to test hypotheses for the enzyme mechanism. The results will provide a basis for the future manipulation of the enzymes' activities. Our other targets, sulfocyanin and auracyanin-A, perform essential electron-transfer functions in an archaeon and a photosynthetic bacterium, respectively. The determination of their molecular structures will answer exciting questions about electron transfer in primitive organisms, and about the evolution of copper proteins as biological electron-transfer agents.Read moreRead less
Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosph ....Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosphate ester bonds in biological molecules will be developed. Active complexes will be incorporated into nanosized peptide nucleic acid (PNA) - metal complex hybrids and applied as artificial enzymes in the sequence specific cleavage of RNA and DNA. Novel applications of these ?artificial enzymes? in biotechnology are anticipated.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0344441
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain ....New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain internationally competitive through the application of modern MCD spectroscopic techniques to the study of metal-centred biomolecules. These facilities will drive a number of programs in the area of metalloenzyme and photosystem II research.Read moreRead less