Myelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding and molecular conformation.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is a highly abundant membrane-associated enzyme in the myelin sheath of the vertebrate nervous system. CNPase is a member of the 2H phosphoesterase family and catalyzes the formation of 2'-nucleotide products from 2',3'-cyclic substrates; however, its physiological substrate and function remain unknown. It is likely that CNPase participates in RNA metabolism in the myelinating cell. We solved crystal structures of the phosphodiesterase domain of mouse CNPase, showing the binding mode of nucleotide ligands in the active site. The binding mode of the product 2'-AMP provides a detailed view of the reaction mechanism. Comparisons of CNPase crystal structures highlight flexible loops, which could play roles in substrate recognition; large differences in the active-site vicinity are observed when comparing more distant members of the 2H family. We also studied the full-length CNPase, showing its N-terminal domain is involved in RNA binding and dimerization. Our results provide a detailed picture of the CNPase active site during its catalytic cycle, and suggest a specific function for the previously uncharacterized N-terminal domain.
CitationMyelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding and molecular conformation. 2012, 7 (2):e32336 PLoS ONE
AffiliationDepartment of Biochemistry and Biocenter Oulu, University of Oulu, Oulu, Finland.
The following license files are associated with this item:
- Crystallographic analysis of the reaction cycle of 2',3'-cyclic nucleotide 3'-phosphodiesterase, a unique member of the 2H phosphoesterase family.
- Authors: Myllykoski M, Raasakka A, Lehtimäki M, Han H, Kursula I, Kursula P
- Issue date: 2013 Nov 15
- Determinants of ligand binding and catalytic activity in the myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase.
- Authors: Raasakka A, Myllykoski M, Laulumaa S, Lehtimäki M, Härtlein M, Moulin M, Kursula I, Kursula P
- Issue date: 2015 Nov 13
- Structural similarities and functional differences clarify evolutionary relationships between tRNA healing enzymes and the myelin enzyme CNPase.
- Authors: Muruganandam G, Raasakka A, Myllykoski M, Kursula I, Kursula P
- Issue date: 2017 May 16
- The N-terminal domain of 2',3'-cyclic nucleotide 3'-phosphodiesterase harbors a GTP/ATP binding site.
- Authors: Stingo S, Masullo M, Polverini E, Laezza C, Ruggiero I, Arcone R, Ruozi E, Dal Piaz F, Malfitano AM, D'Ursi AM, Bifulco M
- Issue date: 2007 Dec
- Three-dimensional structure of a cyclic-nucleotide phosphodiesterase from human brain.
- Authors: Sakamoto Y, Tanaka N, Ichimiya T, Kurihara T, Nakamura KT
- Issue date: 2004