2c5v: Difference between revisions
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==Overview== | ==Overview== | ||
The cyclin-dependent kinases (CDKs) have been characterized in complex, with a variety of inhibitors, but the majority of structures solved are in, the inactive form. We have solved the structures of six inhibitors in both, the monomeric CDK2 and binary CDK2/cyclinA complexes and demonstrate that, significant differences in ligand binding occur depending on the, activation state. The binding mode of two ligands in particular varies, substantially in active and inactive CDK2. Furthermore, energetic analysis, of CDK2/cyclin/inhibitors demonstrates that a good correlation exists, between the in vitro potency and the calculated energies of interaction, but no such relationship exists for CDK2/inhibitor structures. These, results confirm that monomeric CDK2 ligand complexes do not fully . | The cyclin-dependent kinases (CDKs) have been characterized in complex, with a variety of inhibitors, but the majority of structures solved are in, the inactive form. We have solved the structures of six inhibitors in both, the monomeric CDK2 and binary CDK2/cyclinA complexes and demonstrate that, significant differences in ligand binding occur depending on the, activation state. The binding mode of two ligands in particular varies, substantially in active and inactive CDK2. Furthermore, energetic analysis, of CDK2/cyclin/inhibitors demonstrates that a good correlation exists, between the in vitro potency and the calculated energies of interaction, but no such relationship exists for CDK2/inhibitor structures. These, results confirm that monomeric CDK2 ligand complexes do not fully reflect, active conformations, revealing significant implications for inhibitor, design while also suggesting that the monomeric CDK2 conformation can be, selectively inhibited. | ||
==About this Structure== | ==About this Structure== | ||
2C5V is a | 2C5V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NH2 and CK4 as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 1OKU. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C5V OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:51:05 2007'' | ||
