| Crystal structures of the Helicobacter pylori MTAN enzyme reveal specific interactions between S-adenosylhomocysteine and the 5'-alkylthio binding sub-site. | |
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MedLine Citation:
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PMID: 23148563 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The bacterial 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) enzyme is a multifunctional enzyme that catalyzes the hydrolysis of the N-ribosidic bond of at least four different adenosine-based metabolites: S-adenosylhomocysteine (SAH), 5'methylthioadenosine (MTA), 5'-deoxyadenosine (5'-DOA) and 6-amino-6-deoxyfutalosine. These activities place the enzyme at the hub of seven fundamental bacterial metabolic pathways: S-adenosylmethionine (SAM) utilization, polyamine biosynthesis, the purine salvage pathway, the methionine salvage pathway, the SAM radical pathways, autoinducer-2 biosynthesis and menaquinone biosynthesis. The last pathway makes MTAN essential for H. pylori viability. Although structures of various bacterial and plant MTANs have been described, the interactions between the homocysteine moiety of SAH and the 5'-alkylthiol binding site of MTAN have never been resolved. We have solved crystal structures of an inactive mutant form of Helicobacter pylori MTAN bound to MTA and SAH to 1.63 and 1.20 Å, respectively. The active form of MTAN was also crystallized in the presence of SAH allowing structure determination of a ternary enzyme-product complex resolved at 1.50 Å. These structures identify interactions between the homocysteine moiety and the 5'-alkylthiol binding site of the enzyme. This information can be leveraged for the development of species-specific MTAN inhibitors that prevent the growth of H. pylori. |
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Authors:
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Vidhi Mishra; Donald Robert Ronning |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-13 |
Journal Detail:
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Title: Biochemistry Volume: - ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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