In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-07-16)
Abstract:
Enzymes are proteins that perform reactions that can convert one or more chemicals (the substrates) into others (the products). The rate at which an enzyme produces its product is often carefully regulated. Some molecules slow or stop an enzyme by binding to and blocking the site where its substrates normally bind: its ‘active site’. Other molecules can also bind to sites other than the active site, which can cause the enzyme to become either more or less active. Almost all living things have an enzyme called CTP synthetase that makes one of the building blocks that is used to build DNA and a similar molecule called RNA. This enzyme converts a molecule called uridine triphosphate (or UTP) into another called cytidine triphosphate (CTP): a reaction that is powered by breaking down molecules of adenosine triphosphate (ATP). The amount of CTP synthetase made by a cell is carefully controlled. The enzyme's activity is also regulated by the levels of UTP and CTP, and by another molecule (called GTP) that binds to a site outside of its active site. Four copies of the CTP synthetase protein must work together before this enzyme can turn UTP into CTP. The enzyme also forms much larger aggregates, or polymers; however, it is not clear what causes these polymers to form, or what they do in a cell. Barry et al. have now discovered that CTP synthetase is almost completely inactivated when these polymers are formed. Furthermore, CTP encourages the polymers to form, whilst UTP and ATP cause them to disassemble. Therefore, this enzyme is least active when there is excess product in the cell, and most active when its substrates are plentiful. By determining the three-dimensional structure of a CTP synthetase polymer, Barry et al. reveal that although CTP is bound to the enzymes, their active sites are still freely accessible. However, the enzymes in the polymer appear to be locked into a shape that makes them unable to carry out their function. When Barry et al. then mutated the enzyme so that it was unable to form polymers it was also no longer inactivated in the same way by CTP. Bacterial cells with only these mutant versions of CTP synthetase are unable to properly control their levels of CTP. This suggests that polymer formation is important for regulating this enzyme in response to a build up of its product. Further work is needed to see whether the regulation of CTP synthetase activity by forming polymers is specific to this enzyme or a widespread mechanism that is used to control other enzymes too.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.03638.001
DOI:
10.7554/eLife.03638.002
DOI:
10.7554/eLife.03638.003
DOI:
10.7554/eLife.03638.004
DOI:
10.7554/eLife.03638.005
DOI:
10.7554/eLife.03638.006
DOI:
10.7554/eLife.03638.007
DOI:
10.7554/eLife.03638.008
DOI:
10.7554/eLife.03638.009
DOI:
10.7554/eLife.03638.010
DOI:
10.7554/eLife.03638.011
DOI:
10.7554/eLife.03638.012
DOI:
10.7554/eLife.03638.013
DOI:
10.7554/eLife.03638.014
DOI:
10.7554/eLife.03638.015
DOI:
10.7554/eLife.03638.016
DOI:
10.7554/eLife.03638.017
DOI:
10.7554/eLife.03638.018
DOI:
10.7554/eLife.03638.019
DOI:
10.7554/eLife.03638.020
DOI:
10.7554/eLife.03638.021
DOI:
10.7554/eLife.03638.022
DOI:
10.7554/eLife.03638.023
DOI:
10.7554/eLife.03638.024
DOI:
10.7554/eLife.03638.025
DOI:
10.7554/eLife.03638.026
DOI:
10.7554/eLife.03638.027
DOI:
10.7554/eLife.03638.028
DOI:
10.7554/eLife.03638.029
DOI:
10.7554/eLife.03638.030
DOI:
10.7554/eLife.03638.031
DOI:
10.7554/eLife.03638.032
DOI:
10.7554/eLife.03638.033
DOI:
10.7554/eLife.03638.034
DOI:
10.7554/eLife.03638.035
DOI:
10.7554/eLife.03638.036
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3
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