2v0d
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Virtual screening against a pCDK2/cyclin A crystal structure led to the | + | Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3beta was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Dokurno, P.]] | [[Category: Dokurno, P.]] | ||
| - | [[Category: Murray, J | + | [[Category: Murray, J B.]] |
| - | [[Category: Richardson, C | + | [[Category: Richardson, C M.]] |
| - | [[Category: Surgenor, A | + | [[Category: Surgenor, A E.]] |
[[Category: C53]] | [[Category: C53]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:52:05 2008'' |
Revision as of 16:52, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN CDK2 COMPLEXED WITH A THIAZOLIDINONE INHIBITOR
Overview
Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3beta was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode.
About this Structure
2V0D is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping., Richardson CM, Nunns CL, Williamson DS, Parratt MJ, Dokurno P, Howes R, Borgognoni J, Drysdale MJ, Finch H, Hubbard RE, Jackson PS, Kierstan P, Lentzen G, Moore JD, Murray JB, Simmonite H, Surgenor AE, Torrance CJ, Bioorg Med Chem Lett. 2007 Jul 15;17(14):3880-5. Epub 2007 May 6. PMID:17570665
Page seeded by OCA on Thu Feb 21 18:52:05 2008
Categories: Homo sapiens | Single protein | Dokurno, P. | Murray, J B. | Richardson, C M. | Surgenor, A E. | C53 | CL | Atp-binding | Cdk2 | Cell cycle | Cell division | Cyclin | Kinase | Mitosis | Nucleotide- binding | Nucleotide-binding | Phosphorylation | Serine/threonine-protein kinase | Thiazolidinone ligand | Transferase
