2a8x: Difference between revisions
New page: left|200px<br /><applet load="2a8x" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a8x, resolution 2.40Å" /> '''Crystal Structure of... |
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[[Image:2a8x.gif|left|200px]]<br /><applet load="2a8x" size=" | [[Image:2a8x.gif|left|200px]]<br /><applet load="2a8x" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2a8x, resolution 2.40Å" /> | caption="2a8x, resolution 2.40Å" /> | ||
'''Crystal Structure of Lipoamide Dehydrogenase from Mycobacterium tuberculosis'''<br /> | '''Crystal Structure of Lipoamide Dehydrogenase from Mycobacterium tuberculosis'''<br /> | ||
==Overview== | ==Overview== | ||
We report the 2.4 A crystal structure for lipoamide dehydrogenase encoded | We report the 2.4 A crystal structure for lipoamide dehydrogenase encoded by lpdC from Mycobacterium tuberculosis. Based on the Lpd structure and sequence alignment between bacterial and eukaryotic Lpd sequences, we generated single point mutations in Lpd and assayed the resulting proteins for their ability to catalyze lipoamide reduction/oxidation alone and in complex with other proteins that participate in pyruvate dehydrogenase and peroxidase activities. The results suggest that amino acid residues conserved in mycobacterial species but not conserved in eukaryotic Lpd family members modulate either or both activities and include Arg-93, His-98, Lys-103, and His-386. In addition, Arg-93 and His-386 are involved in forming both "open" and "closed" active site conformations, suggesting that these residues play a role in dynamically regulating Lpd function. Taken together, these data suggest protein surfaces that should be considered while developing strategies for inhibiting this enzyme. | ||
==About this Structure== | ==About this Structure== | ||
2A8X 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 FAD and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydrolipoyl_dehydrogenase Dihydrolipoyl dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.4 1.8.1.4] Full crystallographic information is available from [http:// | 2A8X 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=FAD:'>FAD</scene> and <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydrolipoyl_dehydrogenase Dihydrolipoyl dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.4 1.8.1.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A8X OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bryk, R.]] | [[Category: Bryk, R.]] | ||
[[Category: Buglino, J | [[Category: Buglino, J A.]] | ||
[[Category: Kniewel, R.]] | [[Category: Kniewel, R.]] | ||
[[Category: Lima, C | [[Category: Lima, C D.]] | ||
[[Category: Nathan, C | [[Category: Nathan, C F.]] | ||
[[Category: Rajashankar, K | [[Category: Rajashankar, K R.]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
[[Category: MPD]] | [[Category: MPD]] | ||
[[Category: lipoamide dehydrogenase; pyruvate dehydrogenase; alpha keto acid dehydrogenase; mycobacterium tuberculosis]] | [[Category: lipoamide dehydrogenase; pyruvate dehydrogenase; alpha keto acid dehydrogenase; mycobacterium tuberculosis]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:24:48 2008'' | ||
Revision as of 17:24, 21 February 2008
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Crystal Structure of Lipoamide Dehydrogenase from Mycobacterium tuberculosis
OverviewOverview
We report the 2.4 A crystal structure for lipoamide dehydrogenase encoded by lpdC from Mycobacterium tuberculosis. Based on the Lpd structure and sequence alignment between bacterial and eukaryotic Lpd sequences, we generated single point mutations in Lpd and assayed the resulting proteins for their ability to catalyze lipoamide reduction/oxidation alone and in complex with other proteins that participate in pyruvate dehydrogenase and peroxidase activities. The results suggest that amino acid residues conserved in mycobacterial species but not conserved in eukaryotic Lpd family members modulate either or both activities and include Arg-93, His-98, Lys-103, and His-386. In addition, Arg-93 and His-386 are involved in forming both "open" and "closed" active site conformations, suggesting that these residues play a role in dynamically regulating Lpd function. Taken together, these data suggest protein surfaces that should be considered while developing strategies for inhibiting this enzyme.
About this StructureAbout this Structure
2A8X is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Active as Dihydrolipoyl dehydrogenase, with EC number 1.8.1.4 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis., Rajashankar KR, Bryk R, Kniewel R, Buglino JA, Nathan CF, Lima CD, J Biol Chem. 2005 Oct 7;280(40):33977-83. Epub 2005 Aug 10. PMID:16093239
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