1gu9
From Proteopedia
(New page: 200px<br /><applet load="1gu9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gu9, resolution 1.9Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1gu9.gif|left|200px]]<br /><applet load="1gu9" size=" | + | [[Image:1gu9.gif|left|200px]]<br /><applet load="1gu9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1gu9, resolution 1.9Å" /> | caption="1gu9, resolution 1.9Å" /> | ||
'''CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS ALKYLPEROXIDASE AHPD'''<br /> | '''CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS ALKYLPEROXIDASE AHPD'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The resistance of Mycobacterium tuberculosis to isoniazid is commonly | + | The resistance of Mycobacterium tuberculosis to isoniazid is commonly linked to inactivation of a catalase-peroxidase, KatG, that converts isoniazid to its biologically active form. Loss of KatG is associated with elevated expression of the alkylhydroperoxidases AhpC and AhpD. AhpD has no sequence identity with AhpC or other proteins but has alkylhydroperoxidase activity and possibly additional physiological activities. The alkylhydroperoxidase activity, in the absence of KatG, provides an important antioxidant defense. We have determined the M. tuberculosis AhpD structure to a resolution of 1.9 A. The protein is a trimer in a symmetrical cloverleaf arrangement. Each subunit exhibits a new all-helical protein fold in which the two catalytic sulfhydryl groups, Cys-130 and Cys-133, are located near a central cavity in the trimer. The structure supports a mechanism for the alkylhydroperoxidase activity in which Cys-133 is deprotonated by a distant glutamic acid via the relay action of His-137 and a water molecule. The cysteine then reacts with the peroxide to give a sulfenic acid that subsequently forms a disulfide bond with Cys-130. The crystal structure of AhpD identifies a new protein fold relevant to members of this protein family in other organisms. The structural details constitute a potential platform for the design of inhibitors of potential utility as antitubercular agents and suggest that AhpD may have disulfide exchange properties of importance in other areas of M. tuberculosis biology. |
==About this Structure== | ==About this Structure== | ||
| - | 1GU9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http:// | + | 1GU9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GU9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Djordjevic, S.]] | [[Category: Djordjevic, S.]] | ||
| - | [[Category: Hillas, P | + | [[Category: Hillas, P J.]] |
| - | [[Category: Montellano, P | + | [[Category: Montellano, P R.O De.]] |
[[Category: Nishida, C.]] | [[Category: Nishida, C.]] | ||
| - | [[Category: Nunn, C | + | [[Category: Nunn, C M.]] |
[[Category: alkylhydroperoxidase]] | [[Category: alkylhydroperoxidase]] | ||
[[Category: tuberculosis]] | [[Category: tuberculosis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:00 2008'' |
Revision as of 10:54, 21 February 2008
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CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS ALKYLPEROXIDASE AHPD
Overview
The resistance of Mycobacterium tuberculosis to isoniazid is commonly linked to inactivation of a catalase-peroxidase, KatG, that converts isoniazid to its biologically active form. Loss of KatG is associated with elevated expression of the alkylhydroperoxidases AhpC and AhpD. AhpD has no sequence identity with AhpC or other proteins but has alkylhydroperoxidase activity and possibly additional physiological activities. The alkylhydroperoxidase activity, in the absence of KatG, provides an important antioxidant defense. We have determined the M. tuberculosis AhpD structure to a resolution of 1.9 A. The protein is a trimer in a symmetrical cloverleaf arrangement. Each subunit exhibits a new all-helical protein fold in which the two catalytic sulfhydryl groups, Cys-130 and Cys-133, are located near a central cavity in the trimer. The structure supports a mechanism for the alkylhydroperoxidase activity in which Cys-133 is deprotonated by a distant glutamic acid via the relay action of His-137 and a water molecule. The cysteine then reacts with the peroxide to give a sulfenic acid that subsequently forms a disulfide bond with Cys-130. The crystal structure of AhpD identifies a new protein fold relevant to members of this protein family in other organisms. The structural details constitute a potential platform for the design of inhibitors of potential utility as antitubercular agents and suggest that AhpD may have disulfide exchange properties of importance in other areas of M. tuberculosis biology.
About this Structure
1GU9 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase AhpD, a potential target for antitubercular drug design., Nunn CM, Djordjevic S, Hillas PJ, Nishida CR, Ortiz de Montellano PR, J Biol Chem. 2002 May 31;277(22):20033-40. Epub 2002 Mar 25. PMID:11914371
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