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Three flavonoids targeting the β‐hydroxyacyl‐acyl carrier protein dehydratase from Helicobacter pylori : Crystal structure characterization with enzymatic inhibition assay
Author(s) -
Zhang Liang,
Kong Yunhua,
Wu Dalei,
Zhang Haitao,
Wu Jian,
Chen Jing,
Ding Jianping,
Hu Lihong,
Jiang Hualiang,
Shen Xu
Publication year - 2008
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.036186.108
Subject(s) - apigenin , dehydratase , quercetin , biochemistry , non competitive inhibition , chemistry , enzyme , flavonoid , binding site , stereochemistry , antioxidant
Flavonoids are the major functional components of many herbal and insect preparations and demonstrate varied pharmacological functions including antibacterial activity. Here by enzymatic assay and crystal structure analysis, we studied the inhibition of three flavonoids (quercetin, apigenin, and (S)‐sakuranetin) against the β‐hydroxyacyl‐acyl carrier protein dehydratase from Helicobacter pylori (HpFabZ). These three flavonoids are all competitive inhibitors against HpFabZ by either binding to the entrance of substrate tunnel B (binding model A) or plugging into the tunnel C near the catalytic residues (binding model B) mainly by hydrophobic interaction and hydrogen‐bond pattern. Surrounded by hydrophobic residues of HpFabZ at both positions of models A and B, the methoxy group at C‐7 of (S)‐sakuranetin seems to play an important role for the inhibitor's binding to HpFabZ, partly responsible for the higher inhibitory activity of (S)‐sakuranetin than those of quercetin and apigenin against HpFabZ (IC 50 in μM: (S)‐sakuranetin, 2.0 ± 0.1; quercetin: 39.3 ± 2.7; apigenin, 11.0 ± 2.5). Our work is expected to supply useful information for understanding the potential antibacterial mechanism of flavonoids.