1sj2
From Proteopedia
(New page: 200px<br /><applet load="1sj2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sj2, resolution 2.41Å" /> '''Crystal structure of...) |
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| - | [[Image:1sj2.jpg|left|200px]]<br /><applet load="1sj2" size=" | + | [[Image:1sj2.jpg|left|200px]]<br /><applet load="1sj2" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1sj2, resolution 2.41Å" /> | caption="1sj2, resolution 2.41Å" /> | ||
'''Crystal structure of Mycobacterium tuberculosis catalase-peroxidase'''<br /> | '''Crystal structure of Mycobacterium tuberculosis catalase-peroxidase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Mycobacterium tuberculosis catalase-peroxidase is a multifunctional | + | The Mycobacterium tuberculosis catalase-peroxidase is a multifunctional heme-dependent enzyme that activates the core anti-tuberculosis drug isoniazid. Numerous studies have been undertaken to elucidate the enzyme-dependent mechanism of isoniazid activation, and it is well documented that mutations that reduce activity or inactivate the catalase-peroxidase lead to increased levels of isoniazid resistance in M. tuberculosis. Interpretation of the catalytic activities and the effects of mutations upon the action of the enzyme to date have been limited due to the lack of a three-dimensional structure for this enzyme. In order to provide a more accurate model of the three-dimensional structure of the M. tuberculosis catalase-peroxidase, we have crystallized the enzyme and now report its crystal structure refined to 2.4-A resolution. The structure reveals new information about dimer assembly and provides information about the location of residues that may play a role in catalysis including candidates for protein-based radical formation. Modeling and computational studies suggest that the binding site for isoniazid is located near the delta-meso heme edge rather than in a surface loop structure as currently proposed. The availability of a crystal structure for the M. tuberculosis catalase-peroxidase also permits structural and functional effects of mutations implicated in causing elevated levels of isoniazid resistance in clinical isolates to be interpreted with improved confidence. |
==About this Structure== | ==About this Structure== | ||
| - | 1SJ2 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 HEM and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Catalase Catalase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.6 1.11.1.6] Full crystallographic information is available from [http:// | + | 1SJ2 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=HEM:'>HEM</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Catalase Catalase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.6 1.11.1.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SJ2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bertrand, T.]] | [[Category: Bertrand, T.]] | ||
[[Category: Bodiguel, J.]] | [[Category: Bodiguel, J.]] | ||
| - | [[Category: Brown, K | + | [[Category: Brown, K A.]] |
| - | [[Category: Eady, N | + | [[Category: Eady, N A.J.]] |
[[Category: Jamart-Gregoire, B.]] | [[Category: Jamart-Gregoire, B.]] | ||
[[Category: Jesmin]] | [[Category: Jesmin]] | ||
| - | [[Category: Jones, J | + | [[Category: Jones, J N.]] |
| - | [[Category: Nagy, J | + | [[Category: Nagy, J M.]] |
| - | [[Category: Raven, E | + | [[Category: Raven, E L.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
[[Category: homodimer]] | [[Category: homodimer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:02:03 2008'' |
Revision as of 13:02, 21 February 2008
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Crystal structure of Mycobacterium tuberculosis catalase-peroxidase
Overview
The Mycobacterium tuberculosis catalase-peroxidase is a multifunctional heme-dependent enzyme that activates the core anti-tuberculosis drug isoniazid. Numerous studies have been undertaken to elucidate the enzyme-dependent mechanism of isoniazid activation, and it is well documented that mutations that reduce activity or inactivate the catalase-peroxidase lead to increased levels of isoniazid resistance in M. tuberculosis. Interpretation of the catalytic activities and the effects of mutations upon the action of the enzyme to date have been limited due to the lack of a three-dimensional structure for this enzyme. In order to provide a more accurate model of the three-dimensional structure of the M. tuberculosis catalase-peroxidase, we have crystallized the enzyme and now report its crystal structure refined to 2.4-A resolution. The structure reveals new information about dimer assembly and provides information about the location of residues that may play a role in catalysis including candidates for protein-based radical formation. Modeling and computational studies suggest that the binding site for isoniazid is located near the delta-meso heme edge rather than in a surface loop structure as currently proposed. The availability of a crystal structure for the M. tuberculosis catalase-peroxidase also permits structural and functional effects of mutations implicated in causing elevated levels of isoniazid resistance in clinical isolates to be interpreted with improved confidence.
About this Structure
1SJ2 is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Active as Catalase, with EC number 1.11.1.6 Full crystallographic information is available from OCA.
Reference
Crystal structure of Mycobacterium tuberculosis catalase-peroxidase., Bertrand T, Eady NA, Jones JN, Jesmin, Nagy JM, Jamart-Gregoire B, Raven EL, Brown KA, J Biol Chem. 2004 Sep 10;279(37):38991-9. Epub 2004 Jul 1. PMID:15231843
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