核梭杆菌
没食子酸
生物化学
化学
酶
活动站点
裂解酶
对接(动物)
立体化学
生物
细菌
医学
遗传学
护理部
牙龈卟啉单胞菌
抗氧化剂
作者
Tingting Bu,Jing Lan,Inseong Jo,Jie Zhang,Xue Bai,Shanru He,Xiaoling Jin,Lulu Wang,Junsheng Yu,Xiaoyu Jin,Liying Zhang,Hailong Piao,Nam‐Chul Ha,Chunshan Quan,Ki Hyun Nam,Yongbin Xu
摘要
Fusobacterium nucleatum is a lesion-associated obligate anaerobic pathogen of destructive periodontal disease; it is also implicated in the progression and severity of colorectal cancer. Four genes (FN0625, FN1055, FN1220, and FN1419) of F. nucleatum are involved in producing hydrogen sulfide (H2S), which plays an essential role against oxidative stress. The molecular functions of Fn1419 are known, but their mechanisms remain unclear. We determined the crystal structure of Fn1419 at 2.5 Å, showing the unique conformation of the PLP-binding site when compared with L-methionine γ-lyase (MGL) proteins. Inhibitor screening for Fn1419 with L-cysteine showed that two natural compounds, gallic acid and dihydromyricetin, selectively inhibit the H2S production of Fn1419. The chemicals of gallic acid, dihydromyricetin, and its analogs containing trihydroxybenzene, were potentially responsible for the enzyme-inhibiting activity on Fn1419. Molecular docking and mutational analyses suggested that Gly112, Pro159, Val337, and Arg373 are involved in gallic acid binding and positioned close to the substrate and pyridoxal-5'-phosphate-binding site. Gallic acid has little effect on the other H2S-producing enzymes (Fn1220 and Fn1055). Overall, we proposed a molecular mechanism underlying the action of Fn1419 from F. nucleatum and found a new lead compound for inhibitor development.
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