1hck
From Proteopedia
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| - | [[Image:1hck.gif|left|200px]] | + | [[Image:1hck.gif|left|200px]] |
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| - | '''HUMAN CYCLIN-DEPENDENT KINASE 2''' | + | {{Structure |
| + | |PDB= 1hck |SIZE=350|CAPTION= <scene name='initialview01'>1hck</scene>, resolution 1.9Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''HUMAN CYCLIN-DEPENDENT KINASE 2''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1HCK is a [ | + | 1HCK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HCK OCA]. |
==Reference== | ==Reference== | ||
| - | High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design., Schulze-Gahmen U, De Bondt HL, Kim SH, J Med Chem. 1996 Nov 8;39(23):4540-6. PMID:[http:// | + | High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design., Schulze-Gahmen U, De Bondt HL, Kim SH, J Med Chem. 1996 Nov 8;39(23):4540-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8917641 8917641] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:35:17 2008'' |
Revision as of 09:35, 20 March 2008
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| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN CYCLIN-DEPENDENT KINASE 2
Overview
Inhibition of the cell cycle is widely considered as a new approach toward treatment for diseases caused by unregulated cell proliferation, including cancer. Since cyclin-dependent kinases (CDKs) are key enzymes of cell cycle control, they are promissing targets for the design and discovery of drugs with antiproliferative activity. The detailed structural analysis of CDK2 can provide valuable information for the design of new ligands that can bind in the ATP binding pocket and inhibit CDK2 activity. For this objective, the crystal structures of human CDK2 apoenzyme and its ATP complex were refined to 1.8 and 1.9 A, respectively. The high-resolution refinement reveals 12 ordered water molecules in the ATP binding pocket of the apoenzyme and five ordered waters in that of the ATP complex. Despite a large number of hydrogen bonds between ATP-phosphates and CDK2, binding studies of cyclic AMP-dependent protein kinase with ATP analogues show that the triphosphate moiety contributes little and the adenine ring is most important for binding affinity. Our analysis of CDK2 structural data, hydration of residues in the binding pocket of the apoenzyme, flexibility of the ligand, and structural differences between the apoenzyme and CDK2-ATP complex provide an explanation for the results of earlier binding studies with ATP analogues and a basis for future inhibitor design.
About this Structure
1HCK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design., Schulze-Gahmen U, De Bondt HL, Kim SH, J Med Chem. 1996 Nov 8;39(23):4540-6. PMID:8917641
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