Crystal structure of Haemophilus influenzae 3-isopropylmalate dehydrogenase (LeuB) in complex with the inhibitor O-isobutenyl oxalylhydroxamate

Miggiano, Riccardo; Martignon, S.; Minassi, Alberto; Rossi, Franca; Rizzi, Menico

doi:10.1016/j.bbrc.2020.02.022

Cited by 2 publications

(1 citation statement)

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“…In valine, leucine, and isoleucine biosynthesis, nine DEGs were also significantly downregulated (0.132-fold to 0.331-fold) ( p < 0.05), including a dihydroxy-acid dehydratase ( SAOUHSC_02281 ), an acetolactate synthase large subunit biosynthetic type ( SAOUHSC_02282 ), a conserved hypothetical protein ( SAOUHSC_02283 ), a ketol-acid reductoisomerase ( SAOUHSC_02284 ), a 2-isopropylmalate synthase ( SAOUHSC_02285 ), a 3-isopropylmalate dehydrogenase ( SAOUHSC_02286 ), a 3-isopropylmalate dehydratase large subunit ( SAOUHSC_02287 ), a 3-isopropylmalate dehydratase small subunit ( SAOUHSC_02288 ), and a putative threonine dehydratase ( SAOUHSC_02289 ). For instance, 2-isopropylmalate synthase ( SAOUHSC_02285 , 0.141-fold) catalyzes the first step of leucine biosynthesis and is regulated via feedback inhibition by leucine [ 38 ], while 3-isopropylmalate dehydrogenase ( SAOUHSC_02286 , 0.142-fold) catalyzes the irreversible oxidative decarboxylation of 3-isopropylmalate to 2-ketoisocaproate that is finally converted into leucine by a branched-chain aminotransferase [ 39 ]. Similarly, in arginine biosynthesis, five DEGs were also significantly downregulated (0.246-fold to 0.397-fold) ( p < 0.05), including an acetylglutamate kinase putative ( SAOUHSC_00147 ), a glutamate N-acetyltransferase/amino-acid acetyltransferase ( SAOUHSC_00148 ), an ornithine carbamoyltransferase ( SAOUHSC_01128 ), a carbamate kinase ( SAOUHSC_01129 ), and a nitric oxide synthase oxygenase domain putative ( SAOUHSC_02134 ).…”

Section: Resultsmentioning

confidence: 99%

Antibacterial Components and Modes of the Methanol-Phase Extract from Commelina communis Linn

Liu

Tang

Chen

2023

Plants

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Infectious diseases caused by pathogenic bacteria severely threaten human health. Traditional Chinese herbs are potential sources of new or alternative medicine. In this study, we analyzed for the first time antibacterial substances in the methanol-phase extract from a traditional Chinese herb—Commelina communis Linn—which showed an inhibition rate of 58.33% against 24 species of common pathogenic bacteria. The extract was further purified using preparative high-performance liquid chromatography (Prep-HPLC), which generated four single fragments (Fragments 1 to 4). The results revealed that Fragment 1 significantly increased bacterial cell surface hydrophobicity and membrane permeability and decreased membrane fluidity, showing disruptive effects on cell integrity of Gram-positive and Gram-negative bacteria, such as Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, and Salmonella enterica subsp., compared to the control groups (p < 0.05). In sum, 65 compounds with known functions in Fragment 1 were identified using liquid chromatography and mass spectrometry (LC-MS), of which quercetin-3-o-glucuronide was predominant (19.35%). Comparative transcriptomic analysis revealed multiple altered metabolic pathways mediated by Fragment 1, such as inhibited ABC transporters, ribosome, citrate cycle and oxidative phosphorylation, and upregulated nitrogen metabolism and purine metabolism, thereby resulting in the repressed bacterial growth and even death (p < 0.05). Overall, the results of this study demonstrate that Fragment 1 from C. communis Linn is a promising candidate against common pathogenic bacteria.

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Section: Resultsmentioning

confidence: 99%