2i53
From Proteopedia
|
Crystal structure of Cyclin K
Overview
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.
About this Structure
2I53 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of human cyclin K, a positive regulator of cyclin-dependent kinase 9., Baek K, Brown RS, Birrane G, Ladias JA, J Mol Biol. 2007 Feb 16;366(2):563-73. Epub 2006 Nov 18. PMID:17169370
Page seeded by OCA on Fri Feb 15 17:34:51 2008
