3ep5

Human AdoMetDC E178Q mutant with no putrescine bound

spinqualitylabelsall models 3ep5, resolution 1.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ep5 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 1.99Å Ligands: PYR, TRS, URE 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 Putrescine (1,4-diaminobutane) activates the autoprocessing and decarboxylation reactions of human S-adenosylmethionine decarboxylase (AdoMetDC), a critical enzyme in the polyamine biosynthetic pathway. In human AdoMetDC, putrescine binds in a buried pocket containing acidic residues Asp174, Glu178, and Glu256. The pocket is away from the active site but near the dimer interface; however, a series of hydrophilic residues connect the putrescine binding site and the active site. Mutation of these acidic residues modulates the effects of putrescine. D174N, E178Q, and E256Q mutants were expressed and dialyzed to remove putrescine and studied biochemically using X-ray crystallography, UV-CD spectroscopy, analytical ultracentrifugation, and ITC binding studies. The results show that the binding of putrescine to the wild type dimeric protein is cooperative. The D174N mutant does not bind putrescine, and the E178Q and E256Q mutants bind putrescine weakly with no cooperativity. The crystal structure of the mutants with and without putrescine and their complexes with S-adenosylmethionine methyl ester were obtained. Binding of putrescine results in a reorganization of four aromatic residues (Phe285, Phe315, Tyr318, and Phe320) and a conformational change in the loop 312-320. The loop shields putrescine from the external solvent, enhancing its electrostatic and hydrogen bonding effects. The E256Q mutant with putrescine added shows an alternate conformation of His243, Glu11, Lys80, and Ser229, the residues that link the active site and the putrescine binding site, suggesting that putrescine activates the enzyme through electrostatic effects and acts as a switch to correctly orient key catalytic residues. Structural basis for putrescine activation of human S-adenosylmethionine decarboxylase.,Bale S, Lopez MM, Makhatadze GI, Fang Q, Pegg AE, Ealick SE Biochemistry. 2008 Dec 16;47(50):13404-17. PMID:19053272 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also SAM decarboxylase

Proteopedia Page Contributors and Editors (what is this?)

OCA