Asset Details
Do you wish to reserve the book?
Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone
Do you wish to request the book?
Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone
2015
Overview
Nucleotide-based second messengers serve in the response of living organisms to environmental changes. In bacteria and plant chloroplasts, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively named “(p)ppGpp”] act as alarmones that globally reprogram cellular physiology during various stress conditions. Enzymes of the RelA/SpoT homology (RSH) family synthesize (p)ppGpp by transferring pyrophosphate from ATP to GDP or GTP. Little is known about the catalytic mechanism and regulation of alarmone synthesis. It also is unclear whether ppGpp and pppGpp execute different functions. Here, we unravel the mechanism and allosteric regulation of the highly cooperative alarmone synthetase small alarmone synthetase 1 (SAS1) fromBacillus subtilis. We determine that the catalytic pathway of (p)ppGpp synthesis involves a sequentially ordered substrate binding, activation of ATP in a strained conformation, and transfer of pyrophosphate through a nucleophilic substitution (SN2) reaction. We show that pppGpp—but not ppGpp—positively regulates SAS1 at an allosteric site. Although the physiological significance remains to be elucidated, we establish the structural and mechanistic basis for a biological activity in which ppGpp and pppGpp execute different functional roles.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Allosteric Regulation - physiology
/ ATP
/ Bacillus subtilis - genetics
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ Chromatography, High Pressure Liquid
/ Chromatography, Ion Exchange
/ Enzymes
/ Guanosine Pentaphosphate - biosynthesis
