4JX3
Crystal structure of Pim1 kinase
Summary for 4JX3
| Entry DOI | 10.2210/pdb4jx3/pdb |
| Related | 4JX7 |
| Descriptor | Serine/threonine-protein kinase pim-1 (2 entities in total) |
| Functional Keywords | human protein kinases, serine/threonine-protein kinase, atp binding, phosphorylation, 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 | 37293.41 |
| Authors | Lee, S.J.,Han, B.G.,Cho, J.W.,Choi, J.S.,Lee, J.K.,Song, H.J.,Koh, J.S.,Lee, B.I. (deposition date: 2013-03-27, release date: 2013-08-28, Last modification date: 2023-09-20) |
| Primary citation | Lee, S.J.,Han, B.G.,Cho, J.W.,Choi, J.S.,Lee, J.,Song, H.J.,Koh, J.S.,Lee, B.I. Crystal structure of pim1 kinase in complex with a pyrido[4,3-d]pyrimidine derivative suggests a unique binding mode. Plos One, 8:e70358-e70358, 2013 Cited by PubMed Abstract: Human Pim1 kinase is a serine/threonine protein kinase that plays important biological roles in cell survival, apoptosis, proliferation, and differentiation. Moreover, Pim1 is up-regulated in various hematopoietic malignancies and solid tumors. Thus, Pim1 is an attractive target for cancer therapeutics, and there has been growing interest in developing small molecule inhibitors for Pim1. Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068). Our inhibitor exhibits a half maximum inhibitory concentration (IC50) of 123 (±14) nM and has an unusual binding mode in complex with Pim1 kinase. The interactions between SKI-O-068 and the Pim1 active site pocket residue are different from those of other scaffold inhibitor-bound structures. The binding mode analysis suggests that the SKI-O-068 inhibitor can be improved by introducing functional groups that facilitate direct interaction with Lys67, which aid in the design of an optimized inhibitor. PubMed: 23936194DOI: 10.1371/journal.pone.0070358 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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