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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.

DOI:10.1021/bi3009664
PMID:22891633
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3437630/
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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d45e/3437630/2612f7d51a2f/nihms401313f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d45e/3437630/18b9a2057ccb/nihms401313f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d45e/3437630/f94ac74568be/nihms401313f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d45e/3437630/2612f7d51a2f/nihms401313f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d45e/3437630/18b9a2057ccb/nihms401313f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d45e/3437630/f94ac74568be/nihms401313f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d45e/3437630/2612f7d51a2f/nihms401313f3.jpg

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1
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J Am Chem Soc. 2012 Jan 25;134(3):1468-70. doi: 10.1021/ja211176q. Epub 2012 Jan 12.
2
The clinical importance of emerging Campylobacter species.新兴弯曲杆菌种的临床重要性。
Nat Rev Gastroenterol Hepatol. 2011 Oct 25;8(12):669-85. doi: 10.1038/nrgastro.2011.191.
3
Enzymatic transition states, transition-state analogs, dynamics, thermodynamics, and lifetimes.
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ACS Infect Dis. 2023 Apr 14;9(4):966-978. doi: 10.1021/acsinfecdis.2c00644. Epub 2023 Mar 15.
4
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FEBS Lett. 2021 Dec;595(24):2995-3005. doi: 10.1002/1873-3468.14223. Epub 2021 Nov 16.
5
Inverse heavy enzyme isotope effects in methylthioadenosine nucleosidases.硫代腺苷甲硫氨酸核苷酶的反重酶同位素效应。
Proc Natl Acad Sci U S A. 2021 Oct 5;118(40). doi: 10.1073/pnas.2109118118.
6
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7
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5
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6
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7
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8
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Nat Chem Biol. 2009 Apr;5(4):251-7. doi: 10.1038/nchembio.153. Epub 2009 Mar 8.