Linked Life Data

21396942

Source:http://linkedlifedata.com/resource/pubmed/id/21396942

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-4-19
pubmed:databankReference
pubmed:abstractText
Cytosolic 5'-nucleotidase II (cN-II) catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates and participates in the regulation of purine nucleotide pools within the cell. It interferes with the phosphorylation-dependent activation of nucleoside analogues used in the treatment of cancer and viral diseases. It is allosterically activated by a number of phosphate-containing cellular metabolites such as ATP, diadenosine polyphosphates, and 2,3-bisphosphoglycerate, which couple its activity with the metabolic state of the cell. We present seven high-resolution structures of human cN-II, including a ligand-free form and complexes with various substrates and effectors. These structures reveal the structural basis for the allosteric activation of cN-II, uncovering a mechanism where an effector-induced disorder-to-order transition generates rearrangements within the catalytic site and the subsequent coordination of the catalytically essential magnesium. Central to the activation is the large transition of the catalytically essential Asp356. This study also provides the structural basis for the substrate specificity of cN-II, where Arg202, Asp206, and Phe157 seem to be important residues for purine/pyrimidine selectivity. These structures provide a comprehensive structural basis for the design of cN-II inhibitors. They also contribute to the understanding of how the nucleotide salvage pathway is regulated at a molecular level.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2011. Published by Elsevier Ltd.
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
408
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
684-96
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structural basis for the allosteric regulation and substrate recognition of human cytosolic 5'-nucleotidase II.
pubmed:affiliation
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't