1lqu
From Proteopedia
(New page: 200px<br /><applet load="1lqu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lqu, resolution 1.25Å" /> '''Mycobacterium tuberc...) |
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| - | [[Image:1lqu.gif|left|200px]]<br /><applet load="1lqu" size=" | + | [[Image:1lqu.gif|left|200px]]<br /><applet load="1lqu" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1lqu, resolution 1.25Å" /> | caption="1lqu, resolution 1.25Å" /> | ||
'''Mycobacterium tuberculosis FprA in complex with NADPH'''<br /> | '''Mycobacterium tuberculosis FprA in complex with NADPH'''<br /> | ||
==Overview== | ==Overview== | ||
| - | FprA is a mycobacterial oxidoreductase that catalyzes the transfer of | + | FprA is a mycobacterial oxidoreductase that catalyzes the transfer of reducing equivalents from NADPH to a protein acceptor. We determined the atomic resolution structure of FprA in the oxidized (1.05 A resolution) and NADPH-reduced (1.25 A resolution) forms. The comparison of these FprA structures with that of bovine adrenodoxin reductase showed no significant overall differences. Hence, these enzymes, which belong to the structural family of the disulfide oxidoreductases, are structurally conserved in very distant organisms such as mycobacteria and mammals. Despite the conservation of the overall fold, the details of the active site of FprA show some peculiar features. In the oxidized enzyme complex, the bound NADP+ exhibits a covalent modification, which has been identified as an oxygen atom linked through a carbonylic bond to the reactive C4 atom of the nicotinamide ring. Mass spectrometry has confirmed this assignment. This NADP+ derivative is likely to form by oxidation of the NADP+ adduct resulting from nucleophilic attack by an active-site water molecule. A Glu-His pair is well positioned to activate the attacking water through a mechanism analogous to that of the catalytic triad in serine proteases. The NADP+ nicotinamide ring exhibits the unusual cis conformation, which may favor derivative formation. The physiological significance of this reaction is presently unknown. However, it could assist with drug-design studies in that the modified NADP+ could serve as a lead compound for the development of specific inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 1LQU 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 ACT, FAD and NDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1LQU 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=ACT:'>ACT</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=NDP:'>NDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LQU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Aliverti, A.]] | [[Category: Aliverti, A.]] | ||
| - | [[Category: Bossi, R | + | [[Category: Bossi, R T.]] |
[[Category: Ferrari, D.]] | [[Category: Ferrari, D.]] | ||
[[Category: Fischer, F.]] | [[Category: Fischer, F.]] | ||
| - | [[Category: Heck, A | + | [[Category: Heck, A J.R.]] |
| - | [[Category: Maier, C | + | [[Category: Maier, C S.]] |
[[Category: Mattevi, A.]] | [[Category: Mattevi, A.]] | ||
[[Category: Raimondi, D.]] | [[Category: Raimondi, D.]] | ||
[[Category: Rizzi, M.]] | [[Category: Rizzi, M.]] | ||
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: Tahallah, N.]] | [[Category: Tahallah, N.]] | ||
[[Category: Zanetti, G.]] | [[Category: Zanetti, G.]] | ||
| Line 38: | Line 38: | ||
[[Category: tuberculosis]] | [[Category: tuberculosis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:47:31 2008'' |
Revision as of 11:47, 21 February 2008
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Mycobacterium tuberculosis FprA in complex with NADPH
Overview
FprA is a mycobacterial oxidoreductase that catalyzes the transfer of reducing equivalents from NADPH to a protein acceptor. We determined the atomic resolution structure of FprA in the oxidized (1.05 A resolution) and NADPH-reduced (1.25 A resolution) forms. The comparison of these FprA structures with that of bovine adrenodoxin reductase showed no significant overall differences. Hence, these enzymes, which belong to the structural family of the disulfide oxidoreductases, are structurally conserved in very distant organisms such as mycobacteria and mammals. Despite the conservation of the overall fold, the details of the active site of FprA show some peculiar features. In the oxidized enzyme complex, the bound NADP+ exhibits a covalent modification, which has been identified as an oxygen atom linked through a carbonylic bond to the reactive C4 atom of the nicotinamide ring. Mass spectrometry has confirmed this assignment. This NADP+ derivative is likely to form by oxidation of the NADP+ adduct resulting from nucleophilic attack by an active-site water molecule. A Glu-His pair is well positioned to activate the attacking water through a mechanism analogous to that of the catalytic triad in serine proteases. The NADP+ nicotinamide ring exhibits the unusual cis conformation, which may favor derivative formation. The physiological significance of this reaction is presently unknown. However, it could assist with drug-design studies in that the modified NADP+ could serve as a lead compound for the development of specific inhibitors.
About this Structure
1LQU is a Single protein structure of sequence from Mycobacterium tuberculosis with , and as ligands. Full crystallographic information is available from OCA.
Reference
A covalent modification of NADP+ revealed by the atomic resolution structure of FprA, a Mycobacterium tuberculosis oxidoreductase., Bossi RT, Aliverti A, Raimondi D, Fischer F, Zanetti G, Ferrari D, Tahallah N, Maier CS, Heck AJ, Rizzi M, Mattevi A, Biochemistry. 2002 Jul 16;41(28):8807-18. PMID:12102623
Page seeded by OCA on Thu Feb 21 13:47:31 2008
Categories: Mycobacterium tuberculosis | Single protein | Aliverti, A. | Bossi, R T. | Ferrari, D. | Fischer, F. | Heck, A J.R. | Maier, C S. | Mattevi, A. | Raimondi, D. | Rizzi, M. | TBSGC, TB Structural Genomics Consortium. | Tahallah, N. | Zanetti, G. | ACT | FAD | NDP | Fad | Nadph | Oxidoreductase | Protein structure initiative | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc | Tuberculosis
