1bu2
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(New page: 200px<br /><applet load="1bu2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bu2, resolution 3.00Å" /> '''X-RAY STRUCTURE OF A...)
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Revision as of 09:48, 20 November 2007
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X-RAY STRUCTURE OF A VIRAL CYCLIN FROM HERPESVIRUS SAIMIRI
Overview
BACKGROUND: Cyclin-dependent kinases (CDKs) have a central role in, cell-cycle control and are activated by complex formation with positive, regulatory proteins called cyclins and by phosphorylation. The, overexpression and mutation of cyclins and CDKs has been associated with, tumorigenesis and oncogenesis. A virus-encoded cyclin (v-cyclin) from, herpesvirus saimiri has been shown to exhibit highest sequence homology to, type D cyclins and specifically activates CDK6 of host cells to a very, high degree. RESULTS: We have determined the first X-ray structure of a, v-cyclin to 3.0 A resolution. The structure of the core domains is very, similar to those of cyclin A and cyclin H from human cells. To understand, the structural basis for the v-cyclin specificity for CDK6 and the, insensitivity of the complex to inhibitors of the p21 and INK4 families, a, v-cyclin-CDK2 model was built on the basis of the known structures of, human cyclin A in complex with CDK2 and the CDK inhibitor p27(Kip1)., CONCLUSIONS: Although many critical interactions between cyclin A and CDK2, would be conserved in a v-cyclin-CDK2 complex, some appear sterically or, electrostatically unfavorable due to shifts in the backbone conformation, or sidechain differences and may contribute to v-cyclin selectivity for, CDK6. The insensitivity of v-cyclin-CDK6 complexes to inhibitors of the, p21 family is probably due to structural changes in v-cyclin that lead to, a flatter surface area offering fewer potential contacts with the protein, inhibitor. In addition, sequence changes in v-cyclin eliminate, hydrogen-bonding partners for atoms of the p27(Kip1) inhibitor. This, structure provides the first model for interactions between v-cyclins and, host cell-cycle proteins; these interactions may be important for virus, survival as well as oncogenic transformation of host cells.
About this Structure
1BU2 is a Single protein structure of sequence from Saimiriine herpesvirus 3. Full crystallographic information is available from OCA.
Reference
Crystal structure of a viral cyclin, a positive regulator of cyclin-dependent kinase 6., Schulze-Gahmen U, Jung JU, Kim SH, Structure. 1999 Mar 15;7(3):245-54. PMID:10368294
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