1jfw

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1jfw

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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 superseeds 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

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