2fum
From Proteopedia
(New page: 200px<br /><applet load="2fum" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fum, resolution 2.89Å" /> '''Catalytic domain of ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2fum.gif|left|200px]]<br /><applet load="2fum" size=" | + | [[Image:2fum.gif|left|200px]]<br /><applet load="2fum" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fum, resolution 2.89Å" /> | caption="2fum, resolution 2.89Å" /> | ||
'''Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone'''<br /> | '''Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mycobacterium tuberculosis PknB is an essential receptor-like protein | + | Mycobacterium tuberculosis PknB is an essential receptor-like protein kinase involved in cell growth control. Here, we demonstrate that mitoxantrone, an anthraquinone derivative used in cancer therapy, is a PknB inhibitor capable of preventing mycobacterial growth. The structure of the complex reveals that mitoxantrone partially occupies the adenine-binding pocket in PknB, providing a framework for the design of compounds with potential therapeutic applications. PknB crystallizes as a 'back-to-back' homodimer identical to those observed in other structures of PknB in complex with ATP analogs. This organization resembles that of the RNA-dependent protein kinase PKR, suggesting a mechanism for kinase activation in mycobacteria. |
==About this Structure== | ==About this Structure== | ||
| - | 2FUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with MIX 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:// | + | 2FUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=MIX:'>MIX</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=2FUM OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Alzari, P | + | [[Category: Alzari, P M.]] |
[[Category: Wehenkel, A.]] | [[Category: Wehenkel, A.]] | ||
[[Category: MIX]] | [[Category: MIX]] | ||
[[Category: protein kinase-inhibitor complex]] | [[Category: protein kinase-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:25:17 2008'' |
Revision as of 15:25, 21 February 2008
|
Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone
Overview
Mycobacterium tuberculosis PknB is an essential receptor-like protein kinase involved in cell growth control. Here, we demonstrate that mitoxantrone, an anthraquinone derivative used in cancer therapy, is a PknB inhibitor capable of preventing mycobacterial growth. The structure of the complex reveals that mitoxantrone partially occupies the adenine-binding pocket in PknB, providing a framework for the design of compounds with potential therapeutic applications. PknB crystallizes as a 'back-to-back' homodimer identical to those observed in other structures of PknB in complex with ATP analogs. This organization resembles that of the RNA-dependent protein kinase PKR, suggesting a mechanism for kinase activation in mycobacteria.
About this Structure
2FUM is a Single protein structure of sequence from Mycobacterium tuberculosis 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
The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria., Wehenkel A, Fernandez P, Bellinzoni M, Catherinot V, Barilone N, Labesse G, Jackson M, Alzari PM, FEBS Lett. 2006 May 29;580(13):3018-22. Epub 2006 Apr 27. PMID:16674948
Page seeded by OCA on Thu Feb 21 17:25:17 2008
