Linked Life Data

21695637

Source:http://linkedlifedata.com/resource/pubmed/id/21695637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
204
pubmed:dateCreated
2011-6-22
pubmed:abstractText
Cyclic nucleotide phosphodiesterases (PDEs) share a highly conserved catalytic domain that hydrolyzes cAMP, cGMP, or both nucleotides. However, the mechanism that allows the PDE catalytic sites to specifically recognize these nucleotides and distinguish between their subtle differences is still unclear. An early model, called the "glutamine switch", proposed that the side chain of an invariant glutamine adopts two different conformations to allow for formation of two hydrogen bonds with cAMP and cGMP, thereby differentiating these nucleotides. However, the structure of PDE4D2 in complex with cAMP shows that Gln369 forms only one hydrogen bond with the substrate. In addition, the structures of PDE10A in complex with cAMP and cGMP reveal that cAMP and cGMP bind to the active site in different orientations and have different interactions with PDE10A residues. These structures suggest that the invariant glutamine does not appear to be a key residue to differentiate between cAMP and cGMP, although it is important for substrate binding. The structure-based sequence alignment shows that most of the active site residues change across PDE families. These residues may not only contribute differently to the substrate specificity, but also generate slightly different shapes and sizes of the active sites in different PDE families. Therefore, the substrate specificity of PDEs is likely to be determined jointly by multiple elements at the active site, yet the detailed mechanism needs further study.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0171-2004
pubmed:author
pubmed:issnType
Print
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
121-34
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structural insight into the substrate specificity of phosphodiesterases.
pubmed:affiliation
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599-7260, USA. hke@med.unc.edu
pubmed:publicationType
Journal Article, Review