1m2q
From Proteopedia
(New page: 200px<br /><applet load="1m2q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m2q, resolution 1.79Å" /> '''Crystal structure of...) |
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| - | [[Image:1m2q.jpg|left|200px]]<br /><applet load="1m2q" size=" | + | [[Image:1m2q.jpg|left|200px]]<br /><applet load="1m2q" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1m2q, resolution 1.79Å" /> | caption="1m2q, resolution 1.79Å" /> | ||
'''Crystal structure of 1,8-di-hydroxy-4-nitro-xanten-9-one/CK2 kinase complex'''<br /> | '''Crystal structure of 1,8-di-hydroxy-4-nitro-xanten-9-one/CK2 kinase complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein kinases play key roles in signal transduction and therefore are | + | Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition. |
==About this Structure== | ==About this Structure== | ||
| - | 1M2Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zea_mays Zea mays] with MNX as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1M2Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zea_mays Zea mays] with <scene name='pdbligand=MNX:'>MNX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M2Q OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Zea mays]] | [[Category: Zea mays]] | ||
[[Category: Battistutta, R.]] | [[Category: Battistutta, R.]] | ||
| - | [[Category: Moliner, E | + | [[Category: Moliner, E De.]] |
[[Category: Moro, S.]] | [[Category: Moro, S.]] | ||
| - | [[Category: Pinna, L | + | [[Category: Pinna, L A.]] |
[[Category: Sarno, S.]] | [[Category: Sarno, S.]] | ||
[[Category: Zagotto, G.]] | [[Category: Zagotto, G.]] | ||
| Line 25: | Line 25: | ||
[[Category: kinase]] | [[Category: kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:50:52 2008'' |
Revision as of 11:50, 21 February 2008
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Crystal structure of 1,8-di-hydroxy-4-nitro-xanten-9-one/CK2 kinase complex
Overview
Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition.
About this Structure
1M2Q is a Single protein structure of sequence from Zea mays with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight., De Moliner E, Moro S, Sarno S, Zagotto G, Zanotti G, Pinna LA, Battistutta R, J Biol Chem. 2003 Jan 17;278(3):1831-6. Epub 2002 Nov 4. PMID:12419810
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