1h0v

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[[Image:1h0v.gif|left|200px]]<br /><applet load="1h0v" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1h0v.gif|left|200px]]
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caption="1h0v, resolution 1.90&Aring;" />
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'''HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[(R)-PYRROLIDINO-5'-YL]METHOXYPURINE'''<br />
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{{Structure
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|PDB= 1h0v |SIZE=350|CAPTION= <scene name='initialview01'>1h0v</scene>, resolution 1.90&Aring;
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|SITE= <scene name='pdbsite=UN4:Un4+Binding+Site+For+Chain+A'>UN4</scene>
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|LIGAND= <scene name='pdbligand=UN4:5-{[(2-AMINO-9H-PURIN-6-YL)OXY]METHYL}-2-PYRROLIDINONE'>UN4</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[(R)-PYRROLIDINO-5'-YL]METHOXYPURINE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1H0V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=UN4:'>UN4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Known structural/functional Site: <scene name='pdbsite=UN4:Un4+Binding+Site+For+Chain+A'>UN4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H0V OCA].
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1H0V 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=1H0V OCA].
==Reference==
==Reference==
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Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives., Gibson AE, Arris CE, Bentley J, Boyle FT, Curtin NJ, Davies TG, Endicott JA, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Mesguiche V, Newell DR, Noble ME, Tucker JA, Whitfield HJ, J Med Chem. 2002 Aug 1;45(16):3381-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12139449 12139449]
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Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives., Gibson AE, Arris CE, Bentley J, Boyle FT, Curtin NJ, Davies TG, Endicott JA, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Mesguiche V, Newell DR, Noble ME, Tucker JA, Whitfield HJ, J Med Chem. 2002 Aug 1;45(16):3381-93. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12139449 12139449]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:56:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:30:37 2008''

Revision as of 09:30, 20 March 2008

Image:1h0v.gif


PDB ID 1h0v

Drag the structure with the mouse to rotate
, resolution 1.90Å
Sites:
Ligands:
Activity: Transferred entry: 2.7.11.1, with EC number 2.7.1.37
Coordinates: save as pdb, mmCIF, xml



HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[(R)-PYRROLIDINO-5'-YL]METHOXYPURINE


Overview

O(6)-substituted guanines are adenosine 5'-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. Fifty-eight O(6)-substituted guanines were prepared to probe the ribose pocket, and the structures of four representative compounds bound to monomeric CDK2 were determined by X-ray crystallography. Optimum binding occurs with a moderately sized aliphatic O(6) substituent that packs tightly against the hydrophobic patch presented by the glycine loop, centered on Val18, an interaction promoted by the conformational restraints imposed in a cyclohexylmethyl or cyclohexenylmethyl ring. Structure-based design generated (R)-(2-amino-9H-purin-6-yloxymethyl)pyrrolidin-2-one (56), which reproduces the reported hydrogen bonds formed between ATP and Asp86 and Gln131 but failed to improve inhibitory potency. Thus, the parent compound O(6)-cyclohexylmethylguanine (NU2058, 25) is the preferred starting point for exploring other areas of the kinase active site.

About this Structure

1H0V is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives., Gibson AE, Arris CE, Bentley J, Boyle FT, Curtin NJ, Davies TG, Endicott JA, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Mesguiche V, Newell DR, Noble ME, Tucker JA, Whitfield HJ, J Med Chem. 2002 Aug 1;45(16):3381-93. PMID:12139449

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