1h0w: Difference between revisions
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[[Image:1h0w.gif|left|200px]]<br /><applet load="1h0w" size=" | [[Image:1h0w.gif|left|200px]]<br /><applet load="1h0w" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1h0w, resolution 2.10Å" /> | caption="1h0w, resolution 2.10Å" /> | ||
'''HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[CYCLOHEX-3-ENYL]METHOXYPURINE'''<br /> | '''HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[CYCLOHEX-3-ENYL]METHOXYPURINE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1H0W 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 207 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=207:207 Binding Site For Chain A'>207</scene>. Full crystallographic information is available from [http:// | 1H0W 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=207:'>207</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=207:207+Binding+Site+For+Chain+A'>207</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H0W OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: protein kinase]] | [[Category: protein kinase]] | ||
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Revision as of 10:44, 3 February 2008
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HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[CYCLOHEX-3-ENYL]METHOXYPURINE
OverviewOverview
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 StructureAbout this Structure
1H0W is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Transferred entry: 2.7.11.1
- Arris, C.E.
- Bentley, J.
- Boyle, F.T.
- Curtin, N.J.
- Davies, T.G.
- Endicott, J.A.
- Gibson, A.E.
- Golding, B.T.
- Grant, S.
- Griffin, R.J.
- Jewsbury, P.
- Johnson, L.N.
- Mesguiche, V.
- Newell, D.R.
- Noble, M.E.M.
- Tucker, J.A.
- Whitfield, H.J.
- 207
- Cell cycle
- Cell division
- Inhibition
- Mitosis
- Phosphorylation
- Protein kinase