This website was created as an assignment for Genetics 564 at the University of Wisconsin-Madison
Chemical genetics of RYR2
Chemical genetics has been classified as an additional tool to investigate many biological functions and processes. Using small molecules to temporarily alter protein expression and function makes chemical genetics an easy yet effective tool in research. Unlike classical genetics, chemical genetics does not require mutation of the gene to activate, inhibit, or alter the protein's function making it a great alternative method. Since many small molecules will be processed and metabolized in the cell, affects of chemical genetics are reversible and allows for quick and easy detection of phenotypic differences induced by the small molecule[1]. Besides understanding the molecular function of various proteins, chemical genetics is commonly used as an technique in drug discovery. Identifying molecules that bind to the protein of interest can be helpful in treating disease, especially if that small molecule produces a desirable phenotype without any other adverse side effects. As chemical genetics has become more popular, chemical libraries such as PubChem or Chembank have been created to provide scientists a database of chemicals that have been already tested experimentally. Some libraries have become so advanced that they are able to predict chemical interactions based on molecular properties and sterics.[2].
PubChem was used to search for compounds that interact with RYR2. Chloroantranilipole was identified in this search as a small molecule that interacted with RYR2 resulting in an activation of calcium mobilization[3]. Chloroantranilipole is used as an insecticide for many different crops, so knowing its effects on RYR2 and heart function is important to know for safety precautions [4]. ChemBank was also used to search small molecules interacting with RYR2, but nothing was found.
Analysis
There are limitations to using databases such as Pubchem or Chembank since they don't have a complete library of chemicals and are based on experiments that have already been performed. Further chemical genetic research should be conducted on proteins interacting with RYR2 since many of these proteins work in conjunction to form the calcium ion complex. Though chemicals identified may not directly interact with RYR2, if it interacts with one of RYR2's binding partners it could have an effect RYR2's function as a result. Another avenue for investigation would be the chemical genetics of proteins involved with the andrenergic pathway. Drug interactions with proteins involved in the andrenergic pathway have been used to treat CPVT since this pathway is responsible for the activation of RYR2. Further investigation of this pathway could provide additional drugs for CPVT treatment.
References:
[1] O’ Connor, Cornelius J. et al. (2011). 40(8) 4332-4340Chemical genetics. Chem Soc Rev. doi:0.1039/c1cs15053g http://pubs.rsc.org/en/content/articlepdf/2011/cs/c1cs15053g
[2]Your World: Biotechnology and You. Searching for Drugs. (1999). 9(1). 12-13. Retrieved April 23, 2014,
from http://www.biotechinstitute.org/download/files/YourWorld/yw-91-computer.pdf
[3]Chloroantranilipole. Retrieved April 27, 2014 from http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=103554006#x321
[4] United States Environmental Protection Agency. (2008).Pesticides Fact Sheet. Retrieved May 1, 2014, from http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_PC-
090100_01-Apr-08.pdf
Chemical Genetics Image- http://galindogen677s12.weebly.com/chemical-genetics.html
[1] O’ Connor, Cornelius J. et al. (2011). 40(8) 4332-4340Chemical genetics. Chem Soc Rev. doi:0.1039/c1cs15053g http://pubs.rsc.org/en/content/articlepdf/2011/cs/c1cs15053g
[2]Your World: Biotechnology and You. Searching for Drugs. (1999). 9(1). 12-13. Retrieved April 23, 2014,
from http://www.biotechinstitute.org/download/files/YourWorld/yw-91-computer.pdf
[3]Chloroantranilipole. Retrieved April 27, 2014 from http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=103554006#x321
[4] United States Environmental Protection Agency. (2008).Pesticides Fact Sheet. Retrieved May 1, 2014, from http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_PC-
090100_01-Apr-08.pdf
Chemical Genetics Image- http://galindogen677s12.weebly.com/chemical-genetics.html
Site created by: Mercede Davis
Email contact: [email protected]
Date last updated: 5/14/14
Genetics 564, University of Wisconsin-Madison
Email contact: [email protected]
Date last updated: 5/14/14
Genetics 564, University of Wisconsin-Madison