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Targeting the Serine Pathway: A Promising Approach against Tuberculosis?

Laboratoire de Chimie Biologique Structurale (CBS), Namur Medicine and Drug Innovation Center (Namedic), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), B-5000 Namur, Belgium
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The submission follows an award given to Marie Haufroid as the best communication at the Journees Franco-Belges de pharmacochimie.
Pharmaceuticals 2019, 12(2), 66; https://doi.org/10.3390/ph12020066
Received: 2 April 2019 / Revised: 24 April 2019 / Accepted: 25 April 2019 / Published: 30 April 2019
Tuberculosis is still the leading cause of death by a single infectious agent. Effective chemotherapy has been used and improved since the 1950s, but strains resistant to this therapy and most antibacterial drugs on the market are emerging. Only 10 new drugs are in clinical trials, and two of them have already demonstrated resistance. This paper gives an overview of current treatment options against tuberculosis and points out a promising approach of discovering new effective drugs. The serine production pathway is composed of three enzymes (SerA1, SerC and SerB2), which are considered essential for bacterial growth, and all of them are considered as a therapeutic drug target. Their crystal structure are described and essential regulatory domains pointed out. Sequence alignment with similar enzymes in other host would help to identify key residues to target in order to achieve selective inhibition. Currently, only inhibitors of SerB2 are described in the literature. However, inhibitors of human enzymes are discussed, and could be used as a good starting point for a drug discovery program. The aim of this paper is to give some guidance for the design of new hits for every enzyme in this pathway. View Full-Text
Keywords: SerB2; phosphoserine phosphatase; HAD; tuberculosis; SerA1; SerC; phosphoserine aminotransferase; phosphoglycerate dehydrogenase SerB2; phosphoserine phosphatase; HAD; tuberculosis; SerA1; SerC; phosphoserine aminotransferase; phosphoglycerate dehydrogenase
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Haufroid, M.; Wouters, J. Targeting the Serine Pathway: A Promising Approach against Tuberculosis? Pharmaceuticals 2019, 12, 66.

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