3dz5

Human AdoMetDC with covalently bound 5'-[(2-aminooxyethyl)methylamino]-5'-deoxy-8-methyladenosine

spinqualitylabelsall models 3dz5, resolution 2.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3dz5 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 2.43Å Ligands: M8M, 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 critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C(8)-substituted adenine analogues bound in the active site. New Insights into the Design of Inhibitors of Human S-Adenosylmethionine Decarboxylase: Studies of Adenine C(8) Substitution in Structural Analogues of S-Adenosylmethionine (dagger).,McCloskey DE, Bale S, Secrist JA, Tiwari A, Moss TH, Valiyaveettil J, Brooks WH, Guida WC, Pegg AE, Ealick SE J Med Chem. 2009 Feb 11. PMID:19209891 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also SAM decarboxylase

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