3F2A
Crystal structure of human Pim-1 in complex with DAPPA
Summary for 3F2A
| Entry DOI | 10.2210/pdb3f2a/pdb |
| Descriptor | Proto-oncogene serine/threonine-protein kinase Pim-1, (2E)-3-{3-[6-(4-methyl-1,4-diazepan-1-yl)pyrazin-2-yl]phenyl}prop-2-enoic acid, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | potein kinase fold, alternative initiation, atp-binding, cell membrane, cytoplasm, kinase, manganese, membrane, metal-binding, nucleotide-binding, nucleus, phosphoprotein, polymorphism, proto-oncogene, serine/threonine-protein kinase, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309 |
| Total number of polymer chains | 1 |
| Total formula weight | 34694.59 |
| Authors | Qian, K. (deposition date: 2008-10-29, release date: 2009-03-10, Last modification date: 2024-10-16) |
| Primary citation | Qian, K.,Wang, L.,Cywin, C.L.,Farmer, B.T.,Hickey, E.,Homon, C.,Jakes, S.,Kashem, M.A.,Lee, G.,Leonard, S.,Li, J.,Magboo, R.,Mao, W.,Pack, E.,Peng, C.,Prokopowicz, A.,Welzel, M.,Wolak, J.,Morwick, T. Hit to lead account of the discovery of a new class of inhibitors of Pim kinases and crystallographic studies revealing an unusual kinase binding mode. J.Med.Chem., 52:1814-1827, 2009 Cited by PubMed Abstract: A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed. PubMed: 19256503DOI: 10.1021/jm801242y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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