4p54

Crystal Structure of the Helicobacter pylori MTAN-D198N mutant with 5'-methylthioadenosine in the active site.

spinqualitylabelsall models 4p54, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p54 is a 1 chain structure with sequence from Campylobacter pylori j99. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, MTA Related: 3nm4, 3nm5, 3nm6, 4ojt, 4oy3 Gene: mtnN, mtn, jhp_0082 (Campylobacter pylori J99) Activity: Adenosylhomocysteine nucleosidase, with EC number 3.2.2.9 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed 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 Helicobacter 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 determined crystal structures of an inactive mutant form of H. pylori MTAN bound to MTA and SAH to 1.63 and 1.20 A, respectively. The active form of MTAN was also crystallized in the presence of SAH, allowing the determination of the structure of a ternary enzyme-product complex resolved at 1.50 A. 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. Crystal structures of the Helicobacter pylori MTAN enzyme reveal specific interactions between S-adenosylhomocysteine and the 5'-alkylthio binding subsite.,Mishra V, Ronning DR Biochemistry. 2012 Dec 4;51(48):9763-72. doi: 10.1021/bi301221k. Epub 2012 Nov, 20. PMID:23148563 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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