Structural highlights
Function
MQMTN_HELPJ Catalyzes the direct conversion of aminodeoxyfutalosine (AFL) into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of the N-glycosidic bond; this reaction seems to represent an essential step in the menaquinone biosynthesis pathway in Helicobacter species. Also catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Can also probably use S-adenosylhomocysteine (SAH) as substrate, leading to adenine and S-ribosylhomocysteine. These other activities highlight the tremendous versatility of the enzyme, which also plays key roles in S-adenosylmethionine recycling and in the biosynthesis of the quorum-sensing molecule autoinducer-2.[1] [2]
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ronning DR, Iacopelli NM, Mishra V. Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase. Protein Sci. 2010 Oct 15. PMID:20954236 doi:10.1002/pro.524
- ↑ Wang S, Haapalainen AM, Yan F, Du Q, Tyler PC, Evans GB, Rinaldo-Matthis A, Brown RL, Norris GE, Almo SC, Schramm VL. A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori. Biochemistry. 2012 Sep 4;51(35):6892-4. Epub 2012 Aug 22. PMID:22891633 doi:http://dx.doi.org/10.1021/bi3009664
- ↑ Wang S, Haapalainen AM, Yan F, Du Q, Tyler PC, Evans GB, Rinaldo-Matthis A, Brown RL, Norris GE, Almo SC, Schramm VL. A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori. Biochemistry. 2012 Sep 4;51(35):6892-4. Epub 2012 Aug 22. PMID:22891633 doi:http://dx.doi.org/10.1021/bi3009664
