D-cycloserine was restructured to treat tuberculosis
December 08, 2017 Source: Sina Pharmaceutical
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â–² Phosphorylated D-cycloserine binds to the complex site of magnesium ion and ADP to the active site of E. coli D-alanine-D alanine ligase
Tuberculosis (TB) remains a global public health threat that is also the leading cause of death worldwide. Therefore, it is essential to find new drugs that effectively control and treat tuberculosis.
A new study by scientists at the University of Warwick and the Francis Crick Institute in the UK will help to more effectively address tuberculosis and other life-threatening microbial infections. The disease, and all of this, is attributed to an ancient antibiotic: D-cylcoserine. The study was recently published online in the top journal Nature Communication, titled: Inhibition of D-Ala: D-Ala Ligase through a Phosphorylated Form of the Antibiotic D-Cycloserine (phosphorylated form) D-cycloserine inhibits D alanine: D alanine ligase), and the findings provide important insights into the design of new antibiotics.
D-cycloserine is an ancient antibiotic that can effectively treat a variety of diseases caused by microbial infections, including tuberculosis, but this drug is often used for second-line treatment due to some side effects.
Interestingly, the researchers found that the antibiotic can act on multiple bacterial targets in a variety of different chemical ways, which is probably the only antibiotic in the world that can act in this way. D-cycloserine attacks bacteria by inhibiting two different enzymes (D-alanine racemase and D-alanine-D alanine ligase), each of which establishes and maintains bacteria Required for structural integrity of the cell wall. In the case of D-alanine racemase, D-cycloserine is capable of forming a molecular bond with a chemical group required for enzymatic activity, which stops the enzyme.
Professor David Roper, the author of the study, said that in this new discovery, we observed that D-cycloserine binds to D-alanine-D alanine ligase and chemically modifies the enzyme to form a chemical species. I have never seen it before. We now fully understand how this antibiotic works in a completely different way for different targets, which may be unique among the antibiotic family. The researchers first observed how D-cycloserine inhibits D-alanine-D-alanine ligase.
Dr. Luiz Pedro Carvolho, head of the Mycobacterium tuberculosis metabolism and antibiotics research group at the Francis Crick Institute, said that perhaps more important than how D-cycloserine works, the study highlights an increasingly obvious fact: Our understanding of the true mode of action of antibiotics is far less than we think. Only by truly understanding the molecular or cellular events triggered by antibiotics or reacting to the presence of antibiotics can we truly understand how to improve drugs, which is urgently needed for the current threat of antibiotic resistance.
The team noted that its long-term goal is to modify the structure of D-cycloserine to bring it closer to newly discovered chemicals, thus developing a new antibiotic that is more specific and avoids the side effects of D-cycloserine. To make it more widely used in the treatment of antibiotic-resistant infections.
With the increasing severity of current antibiotic resistance, there is a global crisis in the field of infectious disease treatment. Antibiotic resistance threatens all aspects of human activity, including medicine and agriculture. Antibiotic resistance may lead to more deaths than cancer. (Sina Pharmaceutical Compilation/newborn)
Article reference source:
1, Old Antibiotic Repurposed to Treat TB
2. Inhibition of D-Ala: D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine
Original title: Ancient antibiotics rejuvenated youth D-cycloserine was restructured to treat tuberculosis
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