This web page was produced as an assignment for Gen677 at UW-Madison Spring 2013
Chemical Genetics
Chemical genetics is the use of small molecules to invesigate biological systems. Small molecules can be used to analyze protein function in a cell in real time by binding and interfering with the protein [1]. Chemical genetics is used to identify small molecules that have medical value or can be tools in biological research to assay particular systems on interest [1].
In a reverse genetics approach a protein of interest can be purified and tested against a chemical library to look for small molecules that interact with it [1]. The identified small molecule can then be added to cell culture or whole animals and a the resulting phenotype assessed. In a forward genetics approach a library of small molecules can be tested against cell types or whole organisms looking for a desired phenotype [1]. The protein that the small molecule the produced the desired phenotype can then be identified [1].
Chembank is an example of a chemical library database of small molecules and their effects on proteins, cell types or whole organisms [2]. The database can be used as a starting point for identifying small molecules of medical value and to identify protein functions and how they relate to cell activity through small molecule inhibition [2]. A NCBI search was done to find a MYO5a interacting small molecule.
In a reverse genetics approach a protein of interest can be purified and tested against a chemical library to look for small molecules that interact with it [1]. The identified small molecule can then be added to cell culture or whole animals and a the resulting phenotype assessed. In a forward genetics approach a library of small molecules can be tested against cell types or whole organisms looking for a desired phenotype [1]. The protein that the small molecule the produced the desired phenotype can then be identified [1].
Chembank is an example of a chemical library database of small molecules and their effects on proteins, cell types or whole organisms [2]. The database can be used as a starting point for identifying small molecules of medical value and to identify protein functions and how they relate to cell activity through small molecule inhibition [2]. A NCBI search was done to find a MYO5a interacting small molecule.
Small Molecule Inhibitor of MYO5a
For MYO5a moves along actin by binding to it and forming an actomyosin complex. It then uses ATP to create motive force. Myovin-1 is a small molecule that inhibits the function of MYO5a by interfering with the release of ADP from the actomyosin complex [3]. This stops MYO5a from using ATP and moving along the actin filament [3].
Analysis
Only approximately 6% of motor proteins have known small molecule inhibitors [3]. Having an effective inhibitor for MYO5a is a potent molecular tool that could be used in a wide variety of experimental designs to study the poorly characterized aspects of MYO5a such as its role in neurons. A better understanding of this role in neuron function could be the first step towards finding a treatment for MYO5a diseases that cause significant neurological defects such as Lavender Foal Syndrome.
References
[1] What is chemical genetics? Genomics and Chemical Genetics - Howard Hughes Medical Institute. Retreived May 15, 2013 from http://www.hhmi.org/biointeractive/genomics/poster_a2.html
[2] Chembank. Retreived May 15, 2013 from http://chembank.broadinstitute.org/welcome.htm
[3] Islam k, Chin HF, Olivares AO, Saunders LP, De La Cruz EM, Kapoor TM. (2010). A Myosin V Inhibitor Based on Privileged Chemical Scaffolds. Angewandte Chemie International Edition. 49(45):8484-8488.
[2] Chembank. Retreived May 15, 2013 from http://chembank.broadinstitute.org/welcome.htm
[3] Islam k, Chin HF, Olivares AO, Saunders LP, De La Cruz EM, Kapoor TM. (2010). A Myosin V Inhibitor Based on Privileged Chemical Scaffolds. Angewandte Chemie International Edition. 49(45):8484-8488.
Rebecca Blackburn, [email protected], 5/15/13