Abstract

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.
Original languageEnglish
JournalPharmaceuticals
Volume12
Issue number2
DOIs
Publication statusPublished - 30 Apr 2019

Fingerprint

Serine
Tuberculosis
Pharmaceutical Preparations
Betahistine
Enzymes
Sequence Alignment
Enzyme Inhibitors
Drug Discovery
Cause of Death
Therapeutics
Clinical Trials
Drug Therapy
Growth

Keywords

  • tuberculosis
  • phosphoserine aminotransferase
  • phosphoserine phosphatase
  • HAD
  • SerC
  • phosphoglycerate dehydrogenase

Cite this

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title = "Targeting the serine pathway : a promising approach against tuberculosis?",
abstract = "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.",
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author = "Marie Haufroid and Johan Wouters",
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Targeting the serine pathway : a promising approach against tuberculosis? / Haufroid, Marie; Wouters, Johan.

In: Pharmaceuticals, Vol. 12, No. 2, 30.04.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Targeting the serine pathway : a promising approach against tuberculosis?

AU - Haufroid, Marie

AU - Wouters, Johan

PY - 2019/4/30

Y1 - 2019/4/30

N2 - 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.

AB - 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.

KW - tuberculosis

KW - phosphoserine aminotransferase

KW - phosphoserine phosphatase

KW - HAD

KW - SerC

KW - phosphoglycerate dehydrogenase

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DO - 10.3390/ph12020066

M3 - Article

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JO - Pharmaceuticals

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SN - 1424-8247

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