1om1
From Proteopedia
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|PDB= 1om1 |SIZE=350|CAPTION= <scene name='initialview01'>1om1</scene>, resolution 1.68Å | |PDB= 1om1 |SIZE=350|CAPTION= <scene name='initialview01'>1om1</scene>, resolution 1.68Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=IQA:(5-OXO-5,6-DIHYDRO-INDOLO[1,2-A]QUINAZOLIN-7-YL)-ACETIC ACID'>IQA</scene> | + | |LIGAND= <scene name='pdbligand=IQA:(5-OXO-5,6-DIHYDRO-INDOLO[1,2-A]QUINAZOLIN-7-YL)-ACETIC+ACID'>IQA</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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1om1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1om1 OCA], [http://www.ebi.ac.uk/pdbsum/1om1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1om1 RCSB]</span> | ||
}} | }} | ||
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[[Category: Moliner, E De.]] | [[Category: Moliner, E De.]] | ||
[[Category: Zanotti, G.]] | [[Category: Zanotti, G.]] | ||
| - | [[Category: IQA]] | ||
[[Category: ck2]] | [[Category: ck2]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
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[[Category: zea may]] | [[Category: zea may]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:47:09 2008'' |
Revision as of 19:47, 30 March 2008
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| , resolution 1.68Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of maize CK2 alpha in complex with IQA
Overview
IQA [[5-oxo-5,6-dihydro-indolo(1,2-a)quinazolin-7-yl]acetic acid] is a novel ATP/GTP site-directed inhibitor of CK2 ('casein kinase 2'), a pleiotropic and constitutively active protein kinase whose activity is abnormally high in transformed cells. The K (i) value of IQA (0.17 microM) is lower than those of other CK2 inhibitors reported so far. Tested at 10 microM concentration in the presence of 100 microM ATP, IQA almost suppresses CK2 activity in vitro, whereas it is ineffective or weakly effective on a panel of 44 protein kinases and on phosphoinositide 3-kinase. In comparison, other CK2 inhibitors, notably apigenin and quercetin, are more promiscuous. The in vivo efficacy of IQA has been assessed by using the fact that treatment of Jurkat cells with IQA inhibits endogenous CK2 in a dose-dependent manner. IQA has been co-crystallized with maize CK2alpha, which is >70% identical with its human homologue, and the structure of the complex has been determined at 1.68 A (1 A=0.1 nm) resolution. The inhibitor lies in the same plane occupied by the purine moiety of ATP with its more hydrophobic side facing the hinge region. Major contributions to the interaction are provided by hydrophobic forces and non-polar interactions involving the aromatic portion of the inhibitor and the hydrophobic residues surrounding the ATP-binding pocket, with special reference to the side chains of V53 (Val53), I66, M163 and I174. Consequently, mutants of human CK2alpha in which either V66 (the homologue of maize CK2alpha I66) or I174 is replaced by alanine are considerably less sensitive to IQA inhibition when compared with wild-type. These results provide new tools for deciphering the enigmatic role of CK2 in living cells and may pave the way for the development of drugs depending on CK2 activity.
About this Structure
1OM1 is a Single protein structure of sequence from Zea mays. Full crystallographic information is available from OCA.
Reference
Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA)., Sarno S, de Moliner E, Ruzzene M, Pagano MA, Battistutta R, Bain J, Fabbro D, Schoepfer J, Elliott M, Furet P, Meggio F, Zanotti G, Pinna LA, Biochem J. 2003 Sep 15;374(Pt 3):639-46. PMID:12816539
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