Mechanisms Underlying The Biochemical Activity Of Scabrosin Esters And Other Epipolythiodioxopiperazine Toxins.
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Fungi produce a variety of chemicals which are toxic to animals. The fungi have probably developed the ability to synthesize and secrete these toxins as part of a chemical defence mechanism and-or in order to limit other microbial life forms because of nutrient competition. Some of these toxins will selectively kill microbes such as bacteria and other fungi as well as simpler life forms such as viruses, which can cause pathological changes to human beings. Fungal toxins may also be useful for co ....Fungi produce a variety of chemicals which are toxic to animals. The fungi have probably developed the ability to synthesize and secrete these toxins as part of a chemical defence mechanism and-or in order to limit other microbial life forms because of nutrient competition. Some of these toxins will selectively kill microbes such as bacteria and other fungi as well as simpler life forms such as viruses, which can cause pathological changes to human beings. Fungal toxins may also be useful for control of proliferative diseases such as cancer. Because fungi have had many millions of years to select for the most efficient toxins, they have been a valuable source of potent toxins for study. Some of these toxins are now in use clinically to treat human diseases ie penicillin and cyclosporin A. A fundamental understanding of fungal toxins is important to ensure the availability of new drugs to combat resistant strains of bacteria and to provide clues for the synthesis of new drugs to treat cancer which can also develop resistance to currently used drugs.Read moreRead less
Snapshots of an enzyme in action: structural and mechanistic studies on the catalytic cycle of Escherichia coli ketol-acid reductoisomerase. Enzymes are required for almost every process that occurs in a living organism. For this reason, understanding how enzymes work is essential if we are to understand life itself. In this project we will investigate the enzyme KARI by capturing a series of snapshots of its atomic structure as it progresses through its working cycle. In addition, we will make ....Snapshots of an enzyme in action: structural and mechanistic studies on the catalytic cycle of Escherichia coli ketol-acid reductoisomerase. Enzymes are required for almost every process that occurs in a living organism. For this reason, understanding how enzymes work is essential if we are to understand life itself. In this project we will investigate the enzyme KARI by capturing a series of snapshots of its atomic structure as it progresses through its working cycle. In addition, we will make a series of small alterations to the atomic structure that will allow us to understand how the individual parts work together.Read moreRead less
Structure and inhibition of acetohydroxyacid synthase. Acetohydroxyacid synthase (AHAS) has been identified as the target for several widely used herbicides known as the sulfonylureas and imidazolinones. World-wide, these two herbicides account for $US2 billion in annual sales. The aim is to determine the three-dimensional structure of AHAS from several sources and in complex with these herbicides. Furthermore, AHAS appears to be an excellent target for the development of antibacterial compounds ....Structure and inhibition of acetohydroxyacid synthase. Acetohydroxyacid synthase (AHAS) has been identified as the target for several widely used herbicides known as the sulfonylureas and imidazolinones. World-wide, these two herbicides account for $US2 billion in annual sales. The aim is to determine the three-dimensional structure of AHAS from several sources and in complex with these herbicides. Furthermore, AHAS appears to be an excellent target for the development of antibacterial compounds and fungicides. Knowledge of the three dimensional structures of these enzymes will be important in the rational design of more effective inhibitors with improved selectivity.Read moreRead less