EC Number   |
Inhibitors |
Structure  |
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    3.5.1.108 | more |
(R)-2-(4-bromophenylsulfonamido)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxypropanamide and (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide show predominantly gram-negative activities, with activities against members of the Enterobacteriaceae, Serratia marcescens, Morganella morganii, Moraxella catarrhalis, Haemophilus influenzae, and Burkholderia cepacia. Neither compound showed activity against Pseudomonas aeruginosa; however, against a leaky Pseudomonas aeruginosa strain, some activity is seen with (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide. (R)-2-(4-bromophenylsulfonamido)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxypropanamide and (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide have little or no activity against the gram-positive bacteria tested |
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| 3.5.1.108 | more |
(4R)-2-(3,4-dimethoxy-5-propylphenyl)-N-hydroxy-4,5-dihydro-1,3-oxazole-4-carboxamide is active against a Pseudomonas aeruginosa construct in which the endogenous lpxC gene is inactivated and in which LpxC activity is supplied by the lpxC gene from Escherichia coli. An Escherichia coli construct in which growth is dependent on the Pseudomonas aeruginosa lpxC gene is resistant to the compound |
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| 3.5.1.108 | more |
incubation of 10 nM LpxC in buffer without bovine serum albumin for 30 min completely inactivates the enzyme. When this enzyme is diluted further (4fold) into buffer containing 1 mg/ml bovine serum albumin, 100% of the activity is restored when assayed after a 2 h incubation. High concentrations of LpxC in the assays can eliminate the requirement of bovine serum albumin |
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| 3.5.1.108 | more |
(S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine, phenyloxazoline hydroxamic acid, competitive inhibitor in Escherichia coli, not active as an antibiotic against Aquifex aeolicus, Pseudomonas aeruginosa and other clinically important pathogens |
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| 3.5.1.108 | more |
the affinity of LpxC for both product and fatty acids is significantly influenced by changes in the number and identity of metal ions bound to the LpxC active site. Therefore, interactions with these metal ions are critical for molecular recognition of ligands by LpxC and may mimic similar contacts with active site inhibitors. These data indicate that the potency of LpxC inhibitors in vitro can be altered by assay conditions used in screening and/or development of LpxC inhibitors and that the metal ion status of LpxC in vivo will likely influence the effectiveness of LpxC inhibitors as antibiotics |
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| 3.5.1.108 | more |
dithiothreitol, glutathione and the C207A mutant prevent the formation of a covalent complex by (E)-2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime; no inhibitory effect by 2,4-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime, 3,4-dimethoxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime, and 2,3,4-trimethoxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime |
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| 3.5.1.108 | more |
mass spectrometry-based screening is a valuable high-throughput screening tool for detecting inhibitors of enzymatic targets involving difficult to detect reactions |
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| 3.5.1.108 | more |
study the potentially important structural differences in active sites of both proteins responsible for making the inhibitors selective for Escherichia coli as compared to Pseudomonas aeruginosa LpxC, homology models of the LpxC of both organisms are developed and validated on the basis of a 3D profile and PROCHECK. Subsequently, a molecular electrostatic potential (MEP)-based surface and cavity-depth analysis is performed. Finally, a cross-docking analysis of reported inhibitors is performed to reveal selective binding modes. These studies identify differences between the two active sites and have implications for designing effective strategies to identify LpxC inhibitors that can be developed as novel broad-spectrum antibacterial drugs |
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| 3.5.1.108 | more |
(S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine and (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide do not inhibit Aquifex aeolicus LpxC |
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| 3.5.1.108 | more |
no evidence of time-dependent inhibition is observed in assays with either the wild-type or mutants |
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