1-deoxy-D-xylulose-5-phosphate synthase from Pseudomonas aeruginosa and Klebsiella pneumoniae reveals conformational changes upon cofactor binding

Hamid, Rawia; Adam, Sebastian; Lacour, Antoine; Monjas, Leticia; Köhnke, Jesko; Hirsch, Anna K.H.

doi:10.1016/j.jbc.2023.105152

Cited by 6 publications

(5 citation statements)

References 36 publications

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“…[3][4][5][6] In the first and rate-limiting step of the MEP pathway, pyruvate and GAP are converted into 1-deoxy-Dxylulose 5-phosphate (DXP) and CO 2 by DXP synthase (DXPS), a thiamine diphosphate (ThDP)-dependent enzyme. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] This makes DXPS an attractive target for the development of antiinfectious agents and herbicides. 5,6 Thus, there have been many studies of DXPS [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and its inhibition.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] This makes DXPS an attractive target for the development of antiinfectious agents and herbicides. 5,6 Thus, there have been many studies of DXPS [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and its inhibition. [23][24][25][26][27][28][29][30][31][32][33] Clomazone (1), a soil-applied herbicide, is effective against grass and broadleaf weeds in many crops.…”

Section: Introductionmentioning

confidence: 99%

“…5–22 This makes DXPS an attractive target for the development of anti-infectious agents and herbicides. 5,6 Thus, there have been many studies of DXPS 7–22 and its inhibition. 23–33…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of ketoclomazone and its analogues as inhibitors of 1-deoxy-d-xylulose 5-phosphate synthases and other thiamine diphosphate (ThDP)-dependent enzymes

Chan,

Ho,

Fathoni

et al. 2024

RSC Med. Chem.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of ketoclomazone and its analogues as inhibitors of 1-deoxy-d-xylulose 5-phosphate synthases and other thiamine diphosphate (ThDP)-dependent enzymes

Chan,

Ho,

Fathoni

et al. 2024

RSC Med. Chem.

Self Cite

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“…[3][4][5][6] In the first and rate-limiting step of the MEP pathway, pyruvate and GAP are converted into 1-deoxy-D-xylulose 5-phosphate (DXP) and CO2 by DXP synthase (DXPS), a thiamine diphosphate (ThDP)-dependent enzyme. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] This makes DXPS an attractive target for the development of anti-infectious agents and herbicides. 5,6 Thus, there have been many studies of DXPS [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and its inhibition [23][24][25][26][27][28][29][30][31][32][33]...…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] This makes DXPS an attractive target for the development of anti-infectious agents and herbicides. 5,6 Thus, there have been many studies of DXPS [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and its inhibition [23][24][25][26][27][28][29][30][31][32][33] . into 2a.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Ketoclomazone and its Analogues as Inhibitors of Thiamine Diphosphate (ThDP)-dependent Enzymes

Chan,

Ho,

Fathoni

et al. 2024

Preprint

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Most pathogenic bacteria, apicomplexan parasites and plants rely on the methylerythritol phosphate (MEP) pathway to obtain precursors of isoprenoids. 1-Deoxy-D-xylulose 5-phosphate synthase (DXPS), a thiamine diphosphate (ThDP)-dependent enzyme, catalyses the first and rate-limiting step of the MEP pathway. Due to its absence in humans, DXPS is considered as an attractive target for the development of anti-infectious agents and herbicides. However, major challenges in designing therapeutic agents that target DXPS include: a) discovering drug-like inhibitors to occupy a highly polar active site; and b) selectively targeting DXPS over other ThDP-dependent enzymes. Ketoclomazone is one of the earliest reported inhibitors of DXPS and antibacterial and herbicidal activities have been documented. This study aimed to investigate the activity of ketoclomazone on DXPS from various species, as well as the broader ThDP-dependent enzyme family. To gain further insights into the inhibition, we have prepared analogues of ketoclomazone and evaluated their activity in biochemical and computational studies. Our findings support the potential of ketoclomazone as a selective antibacterial agent.

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Recent Progress in the Synthesis of α‐Hydroxy Carbonyl Compounds with ThDP‐dependent Carboligases

Dobiašová,

Jurkaš,

Both

et al. 2024

ChemCatChem

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Carboligases catalyze the thiamine diphosphate (ThDP) dependent formation of carbon‐carbon bonds. These enzymes are prominent biocatalysts for the production of valuable a‐hydroxy carbonyl compounds, which serve as key building blocks in the synthesis of various pharmaceuticals and fine chemicals. Carboligases act in selective manner to afford regio‐ and stereochemically defined products from simple starting materials. This review explores the catalytic prowess of carboligases for synthetic purposes and is aimed at providing a selection tool of enzymes for particular sets of substrates or desired products. The comprehensive overview encompasses structural insights, relationships of the currently known sequence space and practical applications with a focus on recent literature, showcasing carboligases as potent tools for sustainable and efficient synthesis.

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1-deoxy-D-xylulose-5-phosphate synthase from Pseudomonas aeruginosa and Klebsiella pneumoniae reveals conformational changes upon cofactor binding

Cited by 6 publications

References 36 publications

Evaluation of ketoclomazone and its analogues as inhibitors of 1-deoxy-d-xylulose 5-phosphate synthases and other thiamine diphosphate (ThDP)-dependent enzymes

Evaluation of ketoclomazone and its analogues as inhibitors of 1-deoxy-d-xylulose 5-phosphate synthases and other thiamine diphosphate (ThDP)-dependent enzymes

Evaluation of Ketoclomazone and its Analogues as Inhibitors of Thiamine Diphosphate (ThDP)-dependent Enzymes

Recent Progress in the Synthesis of α‐Hydroxy Carbonyl Compounds with ThDP‐dependent Carboligases

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