1jfw
From Proteopedia
(New page: 200px<br /> <applet load="1jfw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jfw" /> '''HOMONUCLEAR AND HETERONUCLEAR 1H-13C NUCLEA...) |
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'''HOMONUCLEAR AND HETERONUCLEAR 1H-13C NUCLEAR MAGNETIC RESONANCE ASSIGNMENT AND STRUCTURAL CHARACTERIZATION OF A HIV-1 TAT PROTEIN'''<br /> | '''HOMONUCLEAR AND HETERONUCLEAR 1H-13C NUCLEAR MAGNETIC RESONANCE ASSIGNMENT AND STRUCTURAL CHARACTERIZATION OF A HIV-1 TAT PROTEIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Tat is a viral protein essential for activation of the HIV genes and plays | + | Tat is a viral protein essential for activation of the HIV genes and plays an important role in the HIV-induced immunodeficiency. We chemically synthesized a Tat protein (86 residues) with its six glycines C alpha labelled with 13C. This synthetic protein has the full Tat activity. Heteronuclear nuclear magnetic resonance (NMR) spectra and NOE back-calculation made possible the sequential assignment of the 86 spin systems. Consequently, 915 NMR restraints were identified and 272 of them turned out to be long range ([i-j] > 4), providing structural information on the whole Tat protein. The poor spectral dispersion of Tat NMR spectra does not allow an accurate structure to be determined as for other proteins studied by 2D NMR. Nevertheless, we were able to determine the folding for Tat protein at a 1-mM protein concentration in a 100 mM, pH 4.5 phosphate buffer. The two main Tat functional regions, the basic region and the cysteine-rich region, are well exposed to solvent while a part of the N-terminal region and the C-terminal region constitute the core of Tat Bru. The basic region adopts an extended structure while the cysteine-rich region is made up of two loops. Resolution of this structure was determinant to develop a drug design approach against Tat. The chemical synthesis of the drugs allowed the specific binding and the inhibition of Tat to be verified. |
==About this Structure== | ==About this Structure== | ||
| - | 1JFW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. This structure | + | 1JFW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. This structure supersedes the now removed PDB entry 1FKU. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JFW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Gregoire, C.]] | [[Category: Gregoire, C.]] | ||
[[Category: Opi, S.]] | [[Category: Opi, S.]] | ||
| - | [[Category: Peloponese, J | + | [[Category: Peloponese, J M.]] |
[[Category: drug design]] | [[Category: drug design]] | ||
[[Category: heteronuclear]] | [[Category: heteronuclear]] | ||
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[[Category: tat]] | [[Category: tat]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:22:11 2008'' |
Revision as of 11:22, 21 February 2008
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HOMONUCLEAR AND HETERONUCLEAR 1H-13C NUCLEAR MAGNETIC RESONANCE ASSIGNMENT AND STRUCTURAL CHARACTERIZATION OF A HIV-1 TAT PROTEIN
Overview
Tat is a viral protein essential for activation of the HIV genes and plays an important role in the HIV-induced immunodeficiency. We chemically synthesized a Tat protein (86 residues) with its six glycines C alpha labelled with 13C. This synthetic protein has the full Tat activity. Heteronuclear nuclear magnetic resonance (NMR) spectra and NOE back-calculation made possible the sequential assignment of the 86 spin systems. Consequently, 915 NMR restraints were identified and 272 of them turned out to be long range ([i-j] > 4), providing structural information on the whole Tat protein. The poor spectral dispersion of Tat NMR spectra does not allow an accurate structure to be determined as for other proteins studied by 2D NMR. Nevertheless, we were able to determine the folding for Tat protein at a 1-mM protein concentration in a 100 mM, pH 4.5 phosphate buffer. The two main Tat functional regions, the basic region and the cysteine-rich region, are well exposed to solvent while a part of the N-terminal region and the C-terminal region constitute the core of Tat Bru. The basic region adopts an extended structure while the cysteine-rich region is made up of two loops. Resolution of this structure was determinant to develop a drug design approach against Tat. The chemical synthesis of the drugs allowed the specific binding and the inhibition of Tat to be verified.
About this Structure
1JFW is a Single protein structure of sequence from [1]. This structure supersedes the now removed PDB entry 1FKU. Full crystallographic information is available from OCA.
Reference
1H-13C nuclear magnetic resonance assignment and structural characterization of HIV-1 Tat protein., Peloponese JM Jr, Gregoire C, Opi S, Esquieu D, Sturgis J, Lebrun E, Meurs E, Collette Y, Olive D, Aubertin AM, Witvrow M, Pannecouque C, De Clercq E, Bailly C, Lebreton J, Loret EP, C R Acad Sci III. 2000 Oct;323(10):883-94. PMID:11098404
Page seeded by OCA on Thu Feb 21 13:22:11 2008
Categories: Single protein | Esquieu, D. | Gregoire, C. | Opi, S. | Peloponese, J M. | Drug design | Heteronuclear | Hiv-1 | Tat
