by Kathryn Noakes 41742545
A team of researchers headed by Associate Professor Joseph Wedekind at the University of Rochester Medical Center have determined the structure of a key molecule involved in gene expression in some bacteria, including E. coli, streptococcus and those behind gonorrhea, meningitis and dysentery, which they hope may lead to a new class of antibiotics.
The molecule is called the preQ1 riboswitch. It controls the ability of bacteria to produce ‘queuosine’ (Q), a chemical which is required to overcome an inherent problem in the mRNA-ribosome-tRNA system, known as ‘tRNA wobble’. Without Q, the system is not able to express genes accurately, and the bacteria are unable to produce the products they need to survive and/or cause disease.
Q is formed from the precursor molecules preQ1 and preQ0. preQ0 is converted to preQ1 by the enzyme called queF protein. When in excess, preQ0 bind to preQ1 riboswitches which bind to mRNA molecules that code for the queF protein. The riboswitches modify mRNA’s ribosome binding site, blocking ribosomes and taking away their ability to decode their genetic information. Production of the queF protein is thus inhibited which in turn inhibits production of the preQ1 and Q.
Using X-ray crystallography, researches were able to gain insights into the preQ1 riboswitch structure and its interactions with preQ0. The preQ1 riboswitch folds up into a double helix with bases in its RNA stack on top of each other giving extra stability. The order of bases at one end causes the chain to fold back into a ‘lollipop’ loop. preQ0 then binds to this loop allowing it to bind to the first base of the mRNA’s ribosome binding site, thus locking up the site. They also found that the loop binds to the base in the ribosome binding site using G to C base pairing like that first described by Watson and Crick.
The design of new antibiotics could be based on the base pairs that occur in the riboswitch loop, with the new drugs binding to them in place of the natural signalling molecules, like preQ0. Further investigation will be needed to see what specific base pairs of riboswitches in different bacterial species.
Reference:
University of Rochester Medical Center (2009, April 18). Genetic Switch Potential Key To New Class Of Antibiotics. ScienceDaily. Retrieved April 20, 2009, from http://www.sciencedaily.com /releases/2009/04/090417114435.htm
Extra Links
Science Daily article- links to other articles on the background developments http://www.sciencedaily.com/releases/2009/04/090417114435.htm
The structural basis for recognition of the PreQ0 metabolite by an unusually small riboswitch aptamer domain-original research paper from the J of Bio Chem http://www.ncbi.nlm.nih.gov/pubmed/19261617?dopt=Citation
Joseph E. Wedekind Faculty Page http://dbb.urmc.rochester.edu/bcbp/members/faculty/wedekind_joseph.html
PreQ1 riboswitch. (2008, June 8). In Wikipedia, The Free Encyclopedia. Retrieved 21:23, April 20, 2009, from http://en.wikipedia.org/w/index.php?title=PreQ1_riboswitch&oldid=217952262
