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Crystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori with butyl-thio-DADMe-Immucillin-ACrystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori with butyl-thio-DADMe-Immucillin-A
Structural highlights
Publication Abstract from PubMedCampylobacter 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. A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori.,Wang S, Haapalainen AM, Yan F, Du Q, Tyler PC, Evans GB, Rinaldo-Matthis A, Brown RL, Norris GE, Almo SC, Schramm VL Biochemistry. 2012 Sep 4;51(35):6892-4. Epub 2012 Aug 22. PMID:22891633[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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OCA- Adenosylhomocysteine nucleosidase
- Helicobacter pylori
- Almo, S C.
- Brown, R L.
- Haapalainen, A M.
- Norris, G E.
- Rinaldo-Matthis, A.
- Schramm, V L.
- 5'-methylthioadenosine/s-adenosylhomocysteine nucleosidase
- Acting on glycosyl bond
- Adenosylhomocysteine nucleosidase activity
- Hydrolase
- Hydrolase activity
- L-methionine biosynthetic process from s-adenosylmethionine
- L-methionine salvage from methylthioadenosine
- Methylthioadenosine nucleosidase activity