鈥淎s far as we know, this is the first time that allosteric regulation has been reported for the menaquinone (vitamin K2) biosynthesis pathway in any domain of life,鈥 says lead investigator and Senior Lecturer Dr Jodie Johnston, of UC鈥檚 School of Physical and Chemical Sciences and Biomolecular Interaction Centre.
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(NB: 24 March 2020 is听
A team of New Zealand researchers led by a University of mini传媒 (UC) scientist has discovered a novel mechanism of controlling vitamin K2 production in the bacterial pathogen that causes tuberculosis (known as TB or the white plague).
The finding, which is the cover story of the latest issue of the听, reports that an enzyme called MenD from an early step in the process of making vitamin K2 is controlled by one of the chemicals produced from a later step, just before the vitamin K2 molecule is completed. This so called 鈥渇eedback inhibition鈥 allows the pathogen to slow down or speed up how much vitamin K2 is made (too much or too little is toxic, like Goldilocks they need the amount 鈥渏ust right鈥).
The understanding of how bacterial pathogens like the one that causes TB might control vitamin K2 levels was lacking and this helps scientists understand a key part of that puzzle.
鈥淎s far as we know, this is the first time that allosteric regulation has been reported for the menaquinone (vitamin K2) biosynthesis pathway in any domain of life,鈥 says lead investigator and Senior Lecturer听Dr Jodie Johnston, of UC鈥檚 School of听Physical and Chemical Sciences听and听Biomolecular Interaction Centre.
This ability to control vitamin K2 levels is likely to help the pathogen to adapt to the sometimes hostile and changing environment in the human host during infection. Since humans do not produce vitamin K2, the enzymes that work together to produce it in bacteria are considered possible targets for new antimicrobial drugs. The discovery of this regulation site, and the reporting of the 3D map of that site, provides a new target for creating selective drugs to treat tuberculosis.
The team of Marsden-funded scientists consist of three mid-career researchers with young families, who are all affiliated with the Maurice Wilkins Centre (MWC): lead investigator Dr Jodie Johnston at the University of mini传媒, and Dr Ghader Bashiri and Dr Esther Bulloch both from the School of Biological Sciences at the University of Auckland.
The team combines their biochemical expertise to study bacterial and viral pathogens to reduce the impact of infectious diseases killing millions worldwide per year. They plan to work together in the future to unravel more mysteries about the TB causing pathogen.
Dr Johnston鈥檚 laboratory (supported by mini传媒 Medical Research Foundation and MWC funding) is already tackling work on other pathogens such as the bacteria Staphylococcus aureus, which causes MRSA, a difficult-to-treat infection that most often occurs in healthcare settings.
mini传媒 TB:
On听, it is estimated around 1 in 4 people in the world is infected with this bacterial pathogen and, even 27 years since the WHO declared the disease a global emergency, about 1.5 million people still die from tuberculosis each year. TB remains the world鈥檚 deadliest infectious killer. Each day, over 4000 people lose their lives to TB and close to 30,000 people fall ill with this preventable and curable disease. Global efforts to combat TB have saved an estimated 58 million lives since the year 2000, according to the WHO.
Article URL听
DOI:听10.1074/jbc.RA119.012158
Current Issue (with editor鈥檚 pick highlight link and cover):听
