The general aim of this work is to investigate the three-dimensional structures of important target proteins using X-ray crystallography. Protein crystallography is the study of the three-dimensional shapes of proteins at near atomic resolution. In this method proteins are made to form crystals. X-ray beams are then shone on the crystals causing the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge of the structure of proteins is necessary ....The general aim of this work is to investigate the three-dimensional structures of important target proteins using X-ray crystallography. Protein crystallography is the study of the three-dimensional shapes of proteins at near atomic resolution. In this method proteins are made to form crystals. X-ray beams are then shone on the crystals causing the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge of the structure of proteins is necessary for the complete understanding of their biological activity and is also very useful for the rational design of new drugs that may alter their activity. Approximately one third of the body's proteins are attached to membranes. However, relatively little is known about the three-dimensional structures of this important class of proteins. In this project the structures of proteins that form pores in membrane cell walls are being determined. Some of these proteins are bacterial toxins and knowledge of their structure may prove useful in the design of new antibiotics. Another project involves work on a protein called GABA. The structure of GABA could lead to new drugs that control epilepsy, act as general anaesthetics, relieve anxiety and induce sleep.Read moreRead less
This proposal concerns the biochemical investigation of a protein called GABA receptor which is a known target for various anti-anxiety drugs (anxiolytics), anti-convulsants, sedatives, depressants, anti-epilespy drugs, alcohol and anaesthetics. This work is expected to lead to the determination of the three-dimensional shape of the protein which will provide essential information about how the protein works and lay the foundation for the design and development of new drugs to control epilepsy, ....This proposal concerns the biochemical investigation of a protein called GABA receptor which is a known target for various anti-anxiety drugs (anxiolytics), anti-convulsants, sedatives, depressants, anti-epilespy drugs, alcohol and anaesthetics. This work is expected to lead to the determination of the three-dimensional shape of the protein which will provide essential information about how the protein works and lay the foundation for the design and development of new drugs to control epilepsy, act as general anaesthetics, relieve anxiety and induce sleep.Read moreRead less
Regulation Of Voltage-Gated Potassium Channels: X-ray Structures Of Cytosolic Components Of The BK Nd Kv Families
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
This research will investigate aspects of ion channel gating (opening). Ion channels are specialised pores perforating cell membranes that facilitate transport of ions, or charged atoms, across its breadth. The flow of ions from one side to another is measurable as an electrical current. The pore, or channel, through which ions pass narrows in regions, creating an impasse, or gate , prohibiting passage. The gate is controlled by external factors, such as the binding of certain molecules (ligands ....This research will investigate aspects of ion channel gating (opening). Ion channels are specialised pores perforating cell membranes that facilitate transport of ions, or charged atoms, across its breadth. The flow of ions from one side to another is measurable as an electrical current. The pore, or channel, through which ions pass narrows in regions, creating an impasse, or gate , prohibiting passage. The gate is controlled by external factors, such as the binding of certain molecules (ligands), or, in the case of voltage-dependent ion channels, the application of a voltage to the membrane. Such perturbations widen the pore sufficiently to permit conduction. Voltage-gated potassium channels specifically transport potassium ions. They fall into multiple categories, and generally form large complexes with intracellular, as well as membrane-bound, portions. For some types, cues from intracellular chemical processes are known to regulate electrical excitability, using the intracellular domains to transfer information to the membrane. In others it is not clear if and how this might happen. Our efforts will focus on exploring this theme in two contrasting systems, Kv and BK channels. Kv channels open in response to voltage, whereas activation of BK channels requires both voltage and moderate levels of intracellular calcium. X-ray crystallography will be used to generate accurate three-dimensional images of selected potassium channel components, allowing us to visualise discrete steps in the regulation processes. Potassium channels are essential for life. They effect transmission of our nerve impulses, and are thus fundamental to central nervous system activity. This research will help us to understand the factors that control them.Read moreRead less