3h0v

Human AdoMetDC with 5'-Deoxy-5'-(dimethylsulfonio) adenosine

spinqualitylabelsall models 3h0v, resolution 2.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3h0v is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.24Å Ligands: M2T, PUT, PYR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DCAM_HUMAN Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the polyamine biosynthetic pathway. Inhibition of this pathway and subsequent depletion of polyamine levels is a viable strategy for cancer chemotherapy and for the treatment of parasitic diseases. Substrate analogue inhibitors display an absolute requirement for a positive charge at the position equivalent to the sulfonium of S-adenosylmethionine. We investigated the ligand specificity of AdoMetDC through crystallography, quantum chemical calculations, and stopped-flow experiments. We determined crystal structures of the enzyme cocrystallized with 5'-deoxy-5'-dimethylthioadenosine and 5'-deoxy-5'-(N-dimethyl)amino-8-methyladenosine. The crystal structures revealed a favorable cation-pi interaction between the ligand and the aromatic side chains of Phe7 and Phe223. The estimated stabilization from this interaction is 4.5 kcal/mol as determined by quantum chemical calculations. Stopped-flow kinetic experiments showed that the rate of the substrate binding to the enzyme greatly depends on Phe7 and Phe223, thus supporting the importance of the cation-pi interaction. Role of the Sulfonium Center in Determining the Ligand Specificity of Human S-Adenosylmethionine Decarboxylase.,Bale S, Brooks W, Hanes JW, Mahesan AM, Guida WC, Ealick SE Biochemistry. 2009 Jun 15. PMID:19527050 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also SAM decarboxylase

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