Summary for 5NEV
| Entry DOI | 10.2210/pdb5nev/pdb |
| Descriptor | Cyclin-dependent kinase 2, Cyclin-A2, 4-[[6-(3-phenylphenyl)-7~{H}-purin-2-yl]amino]benzenesulfonamide, ... (4 entities in total) |
| Functional Keywords | cdk2 cyclin a, cdk2 selective transferase, transferase |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941 Nucleus : P20248 |
| Total number of polymer chains | 4 |
| Total formula weight | 129590.05 |
| Authors | Coxon, C.R.,Anscombe, E.,Harnor, S.J.,Martin, M.P.,Carbain, B.,Hardcastle, I.R.,Harlow, L.K.,Korolchuk, S.,Matheson, C.J.,Noble, M.E.M.,Newell, D.R.,Turner, D.,Sivaprakasam, M.,Wang, L.Z.,Wong, C.,Golding, B.T.,Griffin, R.J.,Cano, G. (deposition date: 2017-03-12, release date: 2017-03-29, Last modification date: 2024-10-16) |
| Primary citation | Coxon, C.R.,Anscombe, E.,Harnor, S.J.,Martin, M.P.,Carbain, B.,Golding, B.T.,Hardcastle, I.R.,Harlow, L.K.,Korolchuk, S.,Matheson, C.J.,Newell, D.R.,Noble, M.E.,Sivaprakasam, M.,Tudhope, S.J.,Turner, D.M.,Wang, L.Z.,Wedge, S.R.,Wong, C.,Griffin, R.J.,Endicott, J.A.,Cano, C. Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. J. Med. Chem., 60:1746-1767, 2017 Cited by PubMed Abstract: Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 4-((6-([1,1'-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC 0.044 μM) but was ∼2000-fold less active toward CDK1 (IC 86 μM). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor-kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2. PubMed: 28005359DOI: 10.1021/acs.jmedchem.6b01254 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.97 Å) |
Structure validation
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