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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-3-4
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pubmed:databankReference |
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pubmed:abstractText |
Cyclin from herpesvirus saimiri (Vcyclin) preferentially forms complexes with cyclin-dependent kinase 6 (CDK6) from primate host cells. These complexes show higher kinase activity than host cell CDKs in complex with cellular cyclins and are resistant to cyclin-dependent inhibitory proteins (CDKIs). The crystal structure of human CDK6--Vcyclin in an active state was determined to 3.1 A resolution to better understand the structural basis of CDK6 activation by viral cyclins. The unphosphorylated CDK6 in complex with Vcyclin has many features characteristic of cyclinA-activated, phosphorylated CDK2. There are, however, differences in the conformation at the tip of the T-loop and its interactions with Vcyclin. Residues in the N-terminal extension of Vcyclin wrap around the tip of the CDK6 T-loop and form a short beta-sheet with the T-loop backbone. These interactions lead to a 20% larger buried surface in the CDK6--Vcyclin interface than in the CDK2--cyclinA complex and are probably largely responsible for the specificity of Vcyclin for CDK6 and resistance of the complex to inhibition by INK-type CDKIs.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1072-8368
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
177-81
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11828325-Amino Acid Sequence,
pubmed-meshheading:11828325-Binding Sites,
pubmed-meshheading:11828325-Crystallography, X-Ray,
pubmed-meshheading:11828325-Cyclin-Dependent Kinase 6,
pubmed-meshheading:11828325-Cyclin-Dependent Kinases,
pubmed-meshheading:11828325-Cyclins,
pubmed-meshheading:11828325-Enzyme Activation,
pubmed-meshheading:11828325-Enzyme Inhibitors,
pubmed-meshheading:11828325-Herpesvirus 2, Saimiriine,
pubmed-meshheading:11828325-Humans,
pubmed-meshheading:11828325-Hydrogen Bonding,
pubmed-meshheading:11828325-Models, Molecular,
pubmed-meshheading:11828325-Molecular Sequence Data,
pubmed-meshheading:11828325-Phosphorylation,
pubmed-meshheading:11828325-Protein Binding,
pubmed-meshheading:11828325-Protein Conformation,
pubmed-meshheading:11828325-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11828325-Structure-Activity Relationship,
pubmed-meshheading:11828325-Substrate Specificity,
pubmed-meshheading:11828325-Viral Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
Structural basis for CDK6 activation by a virus-encoded cyclin.
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pubmed:affiliation |
Physical Bioscience Division at E. O. Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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