1jh7
Semi-reduced Inhibitor-bound Cyclic Nucleotide Phosphodiesterase from Arabidopsis thaliana
Structural highlights
FunctionCPD_ARATH Hydrolyzes ADP-ribose 1",2"-cyclic phosphate (Appr>1) that is produced during tRNA splicing into ADP-ribose 1"-phosphate (Appr-1"p). Acts also on nucleoside 2',3'-cyclic phosphates. 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 PubMedThe crystal structure of the semireduced form of cyclic nucleotide phosphodiesterase (CPDase) from Arabidopsis thaliana has been solved by molecular replacement and refined at the resolution of 1.8 A. We have previously reported the crystal structure of the native form of this enzyme, whose main target is ADP-ribose 1",2"-cyclic phosphate, a product of the tRNA splicing reaction. CPDase possesses six cysteine residues, four of which are involved in forming two intra-molecular disulfide bridges. One of these bridges, between Cys-104 and Cys-110, is opened in the semireduced CPDase, whereas the other remains intact. This change of the redox state leads to a conformational rearrangement in the loop covering the active site of the protein. While the native structure shows this partially disordered loop in a coil conformation, in the semireduced enzyme the N-terminal lobe of this loop winds up and elongates the preceding alpha-helix. The semireduced state of CPDase also enabled co-crystallization with a putative inhibitor of its enzymatic activity, 2',3'-cyclic uridine vanadate. The ligand is bound within the active site, and the mode of binding is in agreement with the previously proposed enzymatic mechanism. Selected biophysical properties of the oxidized and the semireduced CPDase are also discussed. Crystal structures of the semireduced and inhibitor-bound forms of cyclic nucleotide phosphodiesterase from Arabidopsis thaliana.,Hofmann A, Grella M, Botos I, Filipowicz W, Wlodawer A J Biol Chem. 2002 Jan 11;277(2):1419-25. Epub 2001 Nov 1. PMID:11694509[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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