作为一种特异性抗生素，针对幽门螺杆菌的 MTAN 的皮摩尔过渡态类似物抑制剂。
A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for Helicobacter pylori.
机构信息
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
出版信息
Biochemistry. 2012 Sep 4;51(35):6892-4. doi: 10.1021/bi3009664. Epub 2012 Aug 22.
Abstract
Campylobacter and Helicobacter species express a 6-amino-6-deoxyfutalosine N-ribosylhydrolase (HpMTAN) proposed to function in menaquinone synthesis. BuT-DADMe-ImmA is a 36 pM transition state analogue of HpMTAN, and the crystal structure of the enzyme-inhibitor complex reveals the mechanism of inhibition. BuT-DADMe-ImmA has a MIC(90) value of <8 ng/mL for Helicobacter pylori growth but does not cause growth arrest in other common clinical pathogens, thus demonstrating potential as an H. pylori-specific antibiotic.
摘要
弯曲菌属和幽门螺杆菌属表达 6-氨基-6-脱氧呋咱核苷 N-核糖基水解酶（HpMTAN），该酶被认为参与了menaquinone 的合成。BuT-DADMe-ImmA 是 HpMTAN 的 36 pM 过渡态类似物，酶-抑制剂复合物的晶体结构揭示了抑制机制。BuT-DADMe-ImmA 对幽门螺杆菌生长的 MIC（90）值<8ng/mL，但不会引起其他常见临床病原体的生长停滞，因此具有作为幽门螺杆菌特异性抗生素的潜力。
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