4bn0
Structure of futalosine hydrolase mutant of Helicobacter pylori strain 26695Structure of futalosine hydrolase mutant of Helicobacter pylori strain 26695
Structural highlights
FunctionMQMTN_HELPY 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. Can also probably catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively. 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. Does not act on futalosine (FL) as substrate.[1] [2] Publication Abstract from PubMedThe recently discovered futalosine pathway is a promising target for the development of new antibiotics. The enzymes involved in this pathway are crucial for the biosynthesis of the essential prokaryotic respiratory compound menaquinone, and as the pathway is limited to few bacterial species such as the gastric pathogen Helicobacter pylori it is a potential target for specific antibiotics. In this report, the crystal structure of an H. pylori methylthioadenosine nucleosidase (MTAN; an enzyme with broad specificity and activity towards 6-amino-6-deoxyfutalosine), which is involved in the second step of menaquinone biosynthesis, has been elucidated at a resolution of 1.76 A and refined with R factors of Rwork = 17% and Rfree = 21%. Activity studies on the wild type and active-site mutants show that the hydrolysis of 6-amino-6-deoxyfutalosine follows a mechanism similar to that of Escherichia coli MTAN. Further evidence for this mode of action is supplied by the crystal structures of active-site mutants. Through the use of reaction intermediates, the structures give additional evidence for the previously proposed nucleosidase mechanism. These structures and the confirmed reaction mechanism will provide a structural basis for the design of new inhibitors targeting the futalosine pathway. Structural enzymology of Helicobacter pylori methylthioadenosine nucleosidase in the futalosine pathway.,Kim RQ, Offen WA, Davies GJ, Stubbs KA Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):177-85. doi:, 10.1107/S1399004713026655. Epub 2013 Dec 31. PMID:24419390[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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