Linked Life Data

16407256

Source:http://linkedlifedata.com/resource/pubmed/id/16407256

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-3-13
pubmed:abstractText
A detailed analysis is presented of the dynamics of human CDK5 in complexes with the protein activator p25 and the purine-like inhibitor roscovitine. These and other findings related to the activation of CDK5 are critically reviewed from a molecular perspective. In addition, the results obtained on the behavior of CDK5 are compared with data on CDK2 to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit association, (iii) conformational changes in the T-loop following CDK/regulatory subunit complex formation, and (iv) specificity in CDK/regulatory subunit recognition. An energy decomposition analysis, used for these purposes, revealed why the binding of p25 alone is sufficient to stabilize the extended active T-loop conformation of CDK5, whereas the equivalent conformational change in CDK2 requires both the binding of cyclin A and phosphorylation of the Thr(160) residue. The interaction energy of the CDK5 T-loop with p25 is about 26 kcal.mol(-1) greater than that of the CDK2 T-loop with cyclin A. The binding pattern between CDK5 and p25 was compared with that of CDK2/cyclin A to find specific regions involved in CDK/regulatory subunit recognition. The analyses performed revealed that the alphaNT-helix of cyclin A interacts with the alpha6-alpha7 loop and the alpha7 helix of CDK2, but these regions do not interact in the CDK5/p25 complex. Further differences between the CDK5/p25 and CDK2/cyclin A systems studied are discussed with respect to their specific functionality.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7271-81
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16407256-Cell Cycle Proteins, pubmed-meshheading:16407256-Cyclin A, pubmed-meshheading:16407256-Cyclin-Dependent Kinase 2, pubmed-meshheading:16407256-Cyclin-Dependent Kinase 5, pubmed-meshheading:16407256-Humans, pubmed-meshheading:16407256-Hydrogen Bonding, pubmed-meshheading:16407256-Models, Chemical, pubmed-meshheading:16407256-Models, Molecular, pubmed-meshheading:16407256-Molecular Conformation, pubmed-meshheading:16407256-Nerve Tissue Proteins, pubmed-meshheading:16407256-Phosphorylation, pubmed-meshheading:16407256-Phylogeny, pubmed-meshheading:16407256-Protein Conformation, pubmed-meshheading:16407256-Protein Kinase Inhibitors, pubmed-meshheading:16407256-Protein Structure, Secondary, pubmed-meshheading:16407256-Protein Structure, Tertiary, pubmed-meshheading:16407256-Purines, pubmed-meshheading:16407256-Stereoisomerism, pubmed-meshheading:16407256-Substrate Specificity, pubmed-meshheading:16407256-Threonine, pubmed-meshheading:16407256-Tyrosine
pubmed:year
2006
pubmed:articleTitle
Different mechanisms of CDK5 and CDK2 activation as revealed by CDK5/p25 and CDK2/cyclin A dynamics.
pubmed:affiliation
Department of Physical Chemistry and Center for Biomolecules and Complex Molecular Systems, Palacký University, tr. Svobody 26, 771 46 Olomouc, Czech Republic. otyepka@aix.upol.cz
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't