2.50
Hdl Handle:
http://hdl.handle.net/10033/271992
Title:
Myelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding and molecular conformation.
Authors:
Myllykoski, Matti; Raasakka, Arne; Han, Huijong; Kursula, Petri
Abstract:
The 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.
Affiliation:
Department of Biochemistry and Biocenter Oulu, University of Oulu, Oulu, Finland.
Citation:
Myelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding and molecular conformation. 2012, 7 (2):e32336 PLoS ONE
Journal:
PloS one
Issue Date:
2012
URI:
http://hdl.handle.net/10033/271992
DOI:
10.1371/journal.pone.0032336
PubMed ID:
22393399
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the research group CSSB

Full metadata record

DC FieldValue Language
dc.contributor.authorMyllykoski, Mattien_GB
dc.contributor.authorRaasakka, Arneen_GB
dc.contributor.authorHan, Huijongen_GB
dc.contributor.authorKursula, Petrien_GB
dc.date.accessioned2013-03-13T08:07:51Z-
dc.date.available2013-03-13T08:07:51Z-
dc.date.issued2012en
dc.identifier.citationMyelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding and molecular conformation. 2012, 7 (2):e32336 PLoS ONEen_GB
dc.identifier.issn1932-6203en
dc.identifier.pmid22393399en
dc.identifier.doi10.1371/journal.pone.0032336en
dc.identifier.urihttp://hdl.handle.net/10033/271992en
dc.description.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.en_GB
dc.language.isoenen
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/226716en]
dc.rightsArchived with thanks to PloS oneen_GB
dc.rightsopenAccessen
dc.subject.mesh2',3'-Cyclic-Nucleotide Phosphodiesterasesen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshCatalysisen_GB
dc.subject.meshCatalytic Domainen_GB
dc.subject.meshCitric Aciden_GB
dc.subject.meshCrystallography, X-Rayen_GB
dc.subject.meshDimerizationen_GB
dc.subject.meshLigandsen_GB
dc.subject.meshMiceen_GB
dc.subject.meshModels, Molecularen_GB
dc.subject.meshMolecular Conformationen_GB
dc.subject.meshMyelin Sheathen_GB
dc.subject.meshProtein Bindingen_GB
dc.subject.meshProtein Structure, Tertiaryen_GB
dc.subject.meshRNAen_GB
dc.subject.meshSulfatesen_GB
dc.titleMyelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding and molecular conformation.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry and Biocenter Oulu, University of Oulu, Oulu, Finland.en_GB
dc.identifier.journalPloS oneen_GB

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