1JFW

HOMONUCLEAR AND HETERONUCLEAR 1H-13C NUCLEAR MAGNETIC RESONANCE ASSIGNMENT AND STRUCTURAL CHARACTERIZATION OF A HIV-1 TAT PROTEIN

Replaces:  1FKU

Summary for 1JFW

• Entry DOI: 10.2210/pdb1jfw/pdb
• Descriptor: TAT PROTEIN (1 entity in total)
• Functional Keywords: tat, hiv-1, heteronuclear, drug design, viral protein
• Cellular location: Host nucleus, host nucleolus: P04610
• Total number of polymer chains: 1
• Total formula weight: 9789.32

Authors

Peloponese, J.M.,Gregoire, C.,Opi, S.,Esquieu, D. (deposition date: 2001-06-22, release date: 2001-08-15, Last modification date: 2024-05-22)

Primary citation

Peloponese Jr., J.M.,Gregoire, C.,Opi, S.,Esquieu, D.,Sturgis, J.,Lebrun, E.,Meurs, E.,Collette, Y.,Olive, D.,Aubertin, A.M.,Witvrow, M.,Pannecouque, C.,De Clercq, E.,Bailly, C.,Lebreton, J.,Loret, E.P.
1H-13C nuclear magnetic resonance assignment and structural characterization of HIV-1 Tat protein.
C.R.Acad.Sci.III, 323:883-894, 2000

PubMed Abstract: 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.

PubMed: 11098404
DOI: 10.1016/S0764-4469(00)01228-2

Experimental method

SOLUTION NMR