1e1v: Difference between revisions

Revision as of 14:33, 2 May 2008

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR NU2058

OverviewOverview

Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition.

About this StructureAbout this Structure

1E1V is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles., Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Garman EF, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Lawrie AM, Newell DR, Noble ME, Sausville EA, Schultz R, Yu W, J Med Chem. 2000 Jul 27;43(15):2797-804. PMID:10956187 Page seeded by OCA on Fri May 2 14:33:18 2008

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OCA

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 [[Image:1e1v.gif|left|200px]]
- {{Structure
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-|PDB= 1e1v |SIZE=350|CAPTION= <scene name='initialview01'>1e1v</scene>, resolution 1.95&Aring;
+The line below this paragraph, containing "STRUCTURE_1e1v", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CMG:6-O-CYCLOHEXYLMETHYL+GUANINE'>CMG</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
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-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e1v OCA], [http://www.ebi.ac.uk/pdbsum/1e1v PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1e1v RCSB]</span>
-}}
 '''HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR NU2058'''
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 [[Category: Johnson, L N.]]
 [[Category: Noble, M E.M.]]
-[[Category: cell cycle]]
+[[Category: Cell cycle]]
-[[Category: cell division]]
+[[Category: Cell division]]
-[[Category: inhibition]]
+[[Category: Inhibition]]
-[[Category: mitosis]]
+[[Category: Mitosis]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: protein kinase]]
+[[Category: Protein kinase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 14:33:18 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:53:22 2008''