5AV0
Crystal structure of DAPK1 in complex with 7,3',4'-trihydroxyisoflavone.
Summary for 5AV0
| Entry DOI | 10.2210/pdb5av0/pdb |
| Related | 5AUT 5AUU 5AUV 5AUW 5AUX 5AUY 5AUZ 5AV1 5AV2 5AV3 5AV4 |
| Descriptor | Death-associated protein kinase 1, 3-(3,4-dihydroxyphenyl)-7-hydroxy-4H-chromen-4-one (3 entities in total) |
| Functional Keywords | death-associated protein kinase 1, serine/threonine protein kinase, natural flavonoid, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 34066.64 |
| Authors | Yokoyama, T.,Mizuguchi, M. (deposition date: 2015-06-10, release date: 2015-10-07, Last modification date: 2024-03-20) |
| Primary citation | Yokoyama, T.,Kosaka, Y.,Mizuguchi, M. Structural Insight into the Interactions between Death-Associated Protein Kinase 1 and Natural Flavonoids. J.Med.Chem., 58:7400-7408, 2015 Cited by PubMed Abstract: Death-associated protein kinase 1 (DAPK1) is a 160 kDa serine/threonine protein kinase that belongs to the Ca(2+)/calmodulin-dependent protein kinase subfamily. DAPK1 is a possible target for the treatment of acute ischemic stroke and endometrial adenocarcinomas. In the present study, we investigated the binding characteristics of 17 natural flavonoids to DAPK1 using a 1-anilinonaphthalene-8-sulfonic acid competitive binding assay and revealed that morin was the strongest binder among the selected compounds. The crystallographic analysis of DAPK1 and 7 selected flavonoid complexes revealed the structure-binding affinity relationship in atomic-level detail. It was suggested that the high affinity of morin could be accounted for by the ionic interaction between 2'-OH and K42 and that such an interaction would not take place with either cyclin-dependent protein kinases or PIM kinases because of their broader entrance regions. Thus, morin would be a more selective inhibitor of DAPK1 than either of these other types of kinases. In addition, we found that the binding of kaempferol to DAPK1 was associated with a chloride ion. The present study provides a better understanding of the molecular properties of the ATP site of DAPK1 and may be useful for the design of specific DAPK1 inhibitors. PubMed: 26322379DOI: 10.1021/acs.jmedchem.5b00893 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
Download full validation report
