Multinuclear NMR and UV–Vis spectroscopy of site directed mutants of the diabetes drug target protein mitoNEET suggest that folding is intimately coupled to iron-sulfur cluster formation
Multinuclear NMR and UV–Vis spectroscopy of site directed mutants of the diabetes drug target protein mitoNEET suggest that folding is intimately coupled to iron-sulfur cluster formation
Publication date: Available online 4 December 2015 Source:Inorganic Chemistry Communications
Author(s): S.K. Benson, K.M. Boyce, R.M. Bunker, N.B. Collins, K.J. Daily, A.S. Esway, G.T. Gilmore, C.W. Hartzler, G.P. Howard, N.A. Kasmar, K.J. Kennedy, B.L. King, T.N. Kordahi, T.A. Mattioli, D.M. Pugh, L.A. Ray, S.L. Ross, M.H. Torcasio, D.P. Webber, D.L. Morris, T.C. Leeper
Further understanding of the mitochondrial protein mitoNEET could lead to advancements in drug design for the treatment of mitochondrial diseases. Previous studies have shown that mitoNEET's iron-sulfur cluster plays a key role in its biochemistry. In order to gain insight into the structural stability and folding of mitoNEET's iron-sulfur clusters, mutants were created using site-directed mutagenesis. NMR and UV–Vis spectroscopic analysis of these mutants suggested that half had successfully hindered protein folding that in turn, increased lability and eventually loss of functional iron-sulfur clusters. Understanding the significance of this coupling of lability to misfolding could be key to learning mitoNEET‘s mode of action in mitochondria. These findings may allow mitoNEET to be utilized for therapeutics and a better understanding of mitochondrial-based diseases. Graphical abstract
[NMR paper] Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies.
Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies.
Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies.
Biochim Biophys Acta. 2014 Nov 22;
Authors: Kim JH, Bothe JR, Reid Alderson T, Markley JL
Abstract
Proteins containing iron-sulfur (Fe-S) clusters arose early in evolution and are essential to life. Organisms have...
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Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies
Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies
Publication date: Available online 22 November 2014
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research</br>
Author(s): Jin Hae Kim , Jameson R. Bothe , T. Reid Alderson , John L. Markley</br>
Proteins containing iron-sulfur (Fe-S) clusters arose early in evolution and are essential to life. Organisms have evolved machinery consisting of specialized proteins that operate together to assemble...
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Solution NMR structure of the iron-sulfur cluster assembly protein U (IscU) with zinc bound at the active site.
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J Mol Biol. 2004 Nov 19;344(2):567-83
Authors: Ramelot TA, Cort JR, Goldsmith-Fischman S, Kornhaber GJ, Xiao R, Shastry R, Acton TB, Honig B, Montelione GT, Kennedy MA
IscU is a highly conserved protein that serves as the scaffold for IscS-mediated assembly of iron-sulfur () clusters. We report the NMR...
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Exploration of the structural environment of the iron-sulfur cluster in putidaredoxin by nitrogen-15 NMR spectroscopy of selectively labeled cysteine residues.
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Authors: Sari N, Holden MJ, Mayhew MP, Vilker VL, Coxon B
Putidaredoxin is a di-iron protein whose paramagnetic region is not well characterized by 1H...
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[NMR paper] 1H NMR of high-potential iron-sulfur protein from the purple non-sulfurbacterium Rhod
1H NMR of high-potential iron-sulfur protein from the purple non-sulfurbacterium Rhodoferax fermentans.
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Eur J Biochem. 1996 Mar 1;236(2):405-11
Authors: Ciurli S, Cremonini MA, Kofod P, Luchinat C
Oxidized and reduced forms of high-potential iron-sulfur protein (HiPIP) from the...
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[NMR paper] Three-dimensional solution structure of the oxidized high potential iron-sulfur prote
Three-dimensional solution structure of the oxidized high potential iron-sulfur protein from Chromatium vinosum through NMR. Comparative analysis with the solution structure of the reduced species.
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Authors: Bertini I, Dikiy A, Kastrau DH, Luchinat C, Sompornpisut P
The NMR solution structure of...
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[NMR paper] The three-dimensional solution structure of the reduced high-potential iron-sulfur pr
The three-dimensional solution structure of the reduced high-potential iron-sulfur protein from Chromatium vinosum through NMR.
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Authors: Banci L, Bertini I, Dikiy A, Kastrau DH, Luchinat C, Sompornpisut P
The 1H NMR assignment of the reduced HiPIP from Chromatium vinosum available in the literature has been extended up to 85% of the total protein protons. Ninety...
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[NMR paper] 1H-NMR investigation of oxidized and reduced high-potential iron-sulfur protein from
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Multinuclear NMR and UV–Vis spectroscopy of site directed mutants of the diabetes drug target protein mitoNEET suggest that folding is intimately coupled to iron-sulfur cluster formation
Linear Mode
