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| {{STRUCTURE_2i53| PDB=2i53 | SCENE= }} | | {{STRUCTURE_2i53| PDB=2i53 | SCENE= }} |
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| '''Crystal structure of Cyclin K'''
| | ===Crystal structure of Cyclin K=== |
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| ==Overview==
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| Cyclin K and the closely related cyclins T1, T2a, and T2b interact with cyclin-dependent kinase 9 (CDK9) forming multiple nuclear complexes, referred to collectively as positive transcription elongation factor b (P-TEFb). Through phosphorylation of the C-terminal domain of the RNA polymerase II largest subunit, distinct P-TEFb species regulate the transcriptional elongation of specific genes that play central roles in human physiology and disease development, including cardiac hypertrophy and human immunodeficiency virus-1 pathogenesis. We have determined the crystal structure of human cyclin K (residues 11-267) at 1.5 A resolution, which represents the first atomic structure of a P-TEFb subunit. The cyclin K fold comprises two typical cyclin boxes with two short helices preceding the N-terminal box. A prominent feature of cyclin K is an additional helix (H4a) in the first cyclin box that obstructs the binding pocket for the cell-cycle inhibitor p27(Kip1). Modeling of CDK9 bound to cyclin K provides insights into the structural determinants underlying the formation and regulation of this complex. A homology model of human cyclin T1 generated using the cyclin K structure as a template reveals that the two proteins have similar structures, as expected from their high level of sequence identity. Nevertheless, their CDK9-interacting surfaces display significant structural differences, which could potentially be exploited for the design of cyclin-targeted inhibitors of the CDK9-cyclin K and CDK9-cyclin T1 complexes.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17169370}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17169370 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17169370}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Positive transcription elongation factor]] | | [[Category: Positive transcription elongation factor]] |
| [[Category: Transcription]] | | [[Category: Transcription]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:04:44 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:43:34 2008'' |
