5VT1
Crystal Structure of the Human CAMKK2B bound to a thiadiazinone benzamide inhibitor
Summary for 5VT1
Entry DOI | 10.2210/pdb5vt1/pdb |
Descriptor | Calcium/calmodulin-dependent protein kinase kinase 2, 4-({5-[(3-hydroxy-4-methylphenyl)amino]-4-oxo-4H-1,2,6-thiadiazin-3-yl}amino)benzamide, MAGNESIUM ION, ... (4 entities in total) |
Functional Keywords | transferase, protein kinase domain, structural genomics, structural genomics consortium, sgc, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
Biological source | Homo sapiens (Human) |
Total number of polymer chains | 1 |
Total formula weight | 33520.95 |
Authors | Counago, R.M.,Asquith, C.R.M.,Arruda, P.,Edwards, A.M.,Gileadi, O.,Kalogirou, A.S.,Koutentis, P.A.,Structural Genomics Consortium (SGC) (deposition date: 2017-05-15, release date: 2017-05-24, Last modification date: 2023-10-04) |
Primary citation | Asquith, C.R.M.,Godoi, P.H.,Counago, R.M.,Laitinen, T.,Scott, J.W.,Langendorf, C.G.,Oakhill, J.S.,Drewry, D.H.,Zuercher, W.J.,Koutentis, P.A.,Willson, T.M.,Kalogirou, A.S. 1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors. Molecules, 23:-, 2018 Cited by PubMed Abstract: We demonstrate for the first time that 4-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors. PubMed: 29783765DOI: 10.3390/molecules23051221 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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