1yi4
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Structure of Pim-1 bound to adenosine
OverviewOverview
Pim-1 is an oncogene-encoded serine/threonine kinase primarily expressed, in hematopoietic and germ cell lines. Pim-1 kinase was originally, identified in Maloney murine leukemia virus-induced T-cell lymphomas and, is associated with multiple cellular functions such as proliferation, survival, differentiation, apoptosis, and tumorigenesis (Wang, Z., Bhattacharya, N., Weaver, M., Petersen, K., Meyer, M., Gapter, L., and, Magnuson, N. S. (2001) J. Vet. Sci. 2, 167-179). The crystal structures of, Pim-1 complexed with staurosporine and adenosine were determined. Although, a typical two-domain serine/threonine protein kinase fold is observed, the, inter-domain hinge region is unusual in both sequence and conformation; a, two-residue insertion causes the hinge to bulge away from the ATP-binding, pocket, and a proline residue in the hinge removes a conserved main chain, hydrogen bond donor. Without this hydrogen bond, van der Waals, interactions with the hinge serve to position the ligand. The hinge region, of Pim-1 resembles that of phosphatidylinositol 3-kinase more closely than, it does other protein kinases. Although the phosphatidylinositol 3-kinase, inhibitor LY294002 also inhibits Pim-1, the structure of the, LY294002.Pim-1 complex reveals a new binding mode that may be general for, Ser/Thr kinases.
About this StructureAbout this Structure
1YI4 is a Single protein structure of sequence from Homo sapiens with ADN as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
ReferenceReference
Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002., Jacobs MD, Black J, Futer O, Swenson L, Hare B, Fleming M, Saxena K, J Biol Chem. 2005 Apr 8;280(14):13728-34. Epub 2005 Jan 17. PMID:15657054
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