6T29
Crystal structure of human calmodulin-dependent protein kinase 1D (CAMK1D) bound to compound 18 (CS587)
This is a non-PDB format compatible entry.
Summary for 6T29
| Entry DOI | 10.2210/pdb6t29/pdb |
| Descriptor | Calcium/calmodulin-dependent protein kinase type 1D, SULFATE ION, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | inhibitor, complex, kinase, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 44113.94 |
| Authors | Kraemer, A.,Sorrell, F.,Butterworth, S.,Edwards, A.M.,Arrowsmith, C.H.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2019-10-08, release date: 2019-11-13, Last modification date: 2024-01-24) |
| Primary citation | Fromont, C.,Atzori, A.,Kaur, D.,Hashmi, L.,Greco, G.,Cabanillas, A.,Nguyen, H.V.,Jones, D.H.,Garzon, M.,Varela, A.,Stevenson, B.,Iacobini, G.P.,Lenoir, M.,Rajesh, S.,Box, C.,Kumar, J.,Grant, P.,Novitskaya, V.,Morgan, J.,Sorrell, F.J.,Redondo, C.,Kramer, A.,Harris, C.J.,Leighton, B.,Vickers, S.P.,Cheetham, S.C.,Kenyon, C.,Grabowska, A.M.,Overduin, M.,Berditchevski, F.,Weston, C.J.,Knapp, S.,Fischer, P.M.,Butterworth, S. Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesityin VivoMouse Model. J.Med.Chem., 63:6784-6801, 2020 Cited by PubMed Abstract: Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first validation of CaMK1D as a target for diabetes therapeutics. PubMed: 32433887DOI: 10.1021/acs.jmedchem.9b01803 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.484 Å) |
Structure validation
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